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124-485: Native Americans named the Paw Paw River after the paw paw fruit that grew abundantly along the river's banks. The watershed includes rare Great Lakes marshes and floodplain forests, which serve as habitats for migratory birds such as the prothonotary warbler (commonly known as the golden swamp warbler ), as well as the endangered Mitchell's satyr butterfly. Other rare species include the massasauga rattlesnake and

248-519: A custard -like texture, and a flavor somewhat similar to banana , mango , and pineapple . They are commonly eaten raw, but are also used to make ice cream and baked desserts. However, the bark, leaves, fruit, and seeds contain the potent neurotoxin annonacin . This plant's scientific name is Asimina triloba. The genus name Asimina is adapted from the Native American (probably Miami-Illinois ) name assimin or rassimin combining

372-423: A exposure are loss of coordination, twitching , convulsions and rapid death by respiratory paralysis . The nerve tissues which communicate with muscles contain a receptor called the nicotinic acetylcholine receptor . Stimulation of these receptors causes a muscular contraction . The anatoxin- a molecule is shaped so it fits this receptor, and in this way it mimics the natural neurotransmitter normally used by

496-444: A metabolite of arsenic, arsenite is formed after ingestion of arsenic and has shown significant toxicity to neurons within about 24 hours of exposure. The mechanism of this cytotoxicity functions through arsenite-induced increases in intracellular calcium ion levels within neurons, which may subsequently reduce mitochondrial transmembrane potential which activates caspases , triggering cell death. Another known function of arsenite

620-475: A treefall gap , owing to the dense shade within a pawpaw patch. Under such circumstances, the pawpaw subcanopy becomes the forest canopy, albeit at a height half as high as the usual canopy of native trees. Accessing full sunlight, the patch is then capable of producing more fruit. Pawpaw is predominantly a lowland species associated with moist but well-drained soils. Recently it has been colonizing drier upland forests. Upslope expansion has been attributed to

744-607: A "pawpaw pollinator watch" in May 2021. Two species of tiny sap beetle were reported as the most abundant and the most consistently present insect types at depth within the flowers, and thus as the most likely effective pollinators. The two species are Glischrochilus quadrisignatus and Stelidota geminata . Both are in the taxonomic family Nitidulidae . Nitidulid beetles are described by Clemson University as likely "night flying" pollinators of pawpaw. Larvae and adult beetle stages of Glischrochilus quadrisignatus were also documented by

868-516: A Jamestown settler transcribed in 1612 as "wheat plum". The Lewis and Clark Expedition consumed pawpaws during their travels. Thomas Jefferson planted it at Monticello , his plantation in Virginia . Legend has it that chilled pawpaw fruit was a favorite dessert of George Washington . Historically, the pawpaw was a commonly-eaten fruit throughout its native range. With the advent of motor travel and refrigeration, it has been used less commonly to

992-433: A banana rather than to Carica papaya . These include wild banana, prairie banana, Indiana banana, Hoosier banana, West Virginia banana, Kansas banana, Kentucky banana, Michigan banana, Missouri banana, Appalachian banana, Ozark banana, Indian banana, banango, and the poor man's banana, as well as American custard apple, asimoya , Quaker delight, and hillbilly mango. Several tribes of Native Americans have terms for

1116-433: A category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a number of ion channels such as calcium, sodium, or potassium channels. In many cases, the toxins released by the different types of cone snails include a range of different types of conotoxins, which may be specific for different ion channels, thus creating a venom capable of widespread nerve function interruption. One of

1240-461: A consequence of increased concentrations, ammonia activity in-vivo has been shown to induce swelling of astrocytes in the brain through increased production of cGMP (Cyclic Guanosine Monophosphate) within the cells which leads to Protein Kinase G-mediated (PKG) cytoskeletal modifications. The resultant effect of this toxicity can be reduced brain energy metabolism and function. Importantly,

1364-514: A deep-reaching taproot . The common pawpaw is the largest and most well known of the 13 species of the Asimina genus in North America. Of those 13, 11 prefer very warm weather and have ranges rarely extending northward of Florida or coastal Alabama. Their ranges do not overlap with Asimina triloba . One southern USA species, Asimina parviflora , does overlap in range with pawpaw. This species

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1488-406: A distinctive imbricated appearance to the tree's foliage. The leaves of the species are simple, alternate and spirally arranged, entire, deciduous , obovate-lanceolate , 10–12 in (25–30 cm) long, 4–5 in (10–13 cm) broad, and wedge-shaped at the base, with an acute apex and an entire margin, with the midrib and primary veins prominent. The petioles are short and stout, with

1612-628: A global (range-wide) scale, the common pawpaw ( A. triloba ) has a NatureServe global conservation rank of G5 (very common). The species is, however, listed for conservation concern in the northernmost parts of its range, owing to the happenstance of where governmental boundaries exist. In the United States, the species has an N5 (very common), but is considered a threatened species in New York, and an endangered species in New Jersey . In Canada , where

1736-422: A greater density of small stems than where the tallest stems have captured the canopy positions. Pawpaws are not the first to colonize a disturbed site, but because they are capable of growing in deep shade, they can establish from seed beneath mature deciduous trees and then spread into a subcanopy patch. They may even become dominant through time by depriving native canopy trees from re-establishing via seed in

1860-428: A high tolerance for intense shading, even compared with other shade-adapted species such as striped maple. Pawpaw leaves cast very heavy shade, and this chokes out seedlings and saplings of most canopy species (though not native spring herbs that benefit from the late-leafing habit of pawpaw).   This helps pawpaw outcompete rival species and is a contributor to its increased abundance in forests across its range. On

1984-535: A lessening of human-set fires within forested habitats of the eastern United States. Unlike common canopy trees such as oaks and pines , pawpaw has no resistance against ground fires. So a reduction in fires has enabled pawpaw, as well as other shade-adapted native trees (including American beech and striped maple ), to become more common. As well, because toxins in the bark, twigs, and leaves of pawpaw repel herbivory, forests browsed by overpopulated deer offer pawpaw even more competitive advantages. Pawpaw exhibits

2108-522: A month later near their northward limit. They have long been a favorite treat throughout the tree's extensive native range in eastern North America, and on occasion are sold locally at farmers' markets . Pawpaw fruits have a sweet, custard-like flavor somewhat similar to banana , mango , and cantaloupe , varying significantly by source or cultivar, with more protein than most fruits. Nineteenth-century American agronomist E. Lewis Sturtevant described pawpaws as "a natural custard, too luscious for

2232-414: A more accurate distinction between true neurotoxins and cytotoxins in an in-vitro testing environment. Due to the significant inaccuracies associated with this process, however, it has been slow in gaining widespread support. Additionally, biochemical mechanisms have become more widely used in neurotoxin testing, such that compounds can be screened for sufficiency to induce cell mechanism interference, like

2356-405: A native species, pawpaw can be planted on river slopes for erosion control, as introduced species formerly used in the eastern United States for this purpose (such as bamboo and Amur honeysuckle ) are now discouraged or prohibited because of their invasiveness . The nonexistent commercial demand of pawpaw timber also protects trees used for ecological reasons from potential future harvest. In

2480-463: A number of potential chemical insults. This barrier creates a tight hydrophobic layer around the capillaries in the brain, inhibiting the transport of large or hydrophilic compounds. In addition to the BBB, the choroid plexus provides a layer of protection against toxin absorption in the brain. The choroid plexuses are vascularized layers of tissue found in the third, fourth, and lateral ventricles of

2604-400: A postsynaptic neuron. The effect of this increased signaling threshold is a reduced excitability of postsynaptic neurons , and subsequent loss of motor and sensory function which can result in paralysis and death. Though assisted ventilation may increase the chance of survival after TTX exposure, there is currently no antitoxin. The use of the acetylcholinesterase inhibitor Neostigmine or

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2728-515: A potential fiber replacement. The planting is occurring several hundred miles north of pawpaw's historically native range, so it is an example of assisted migration of a plant in a time of rapid climate change . Pawpaw logs have been used for split-rail fences in Arkansas . The hard, brown, shiny lima-bean-sized seeds were sometimes carried as pocket pieces in Ohio. Due to the presence of acetogenins,

2852-603: A predator or prey very rapidly, toxins have evolved to become highly specific to their target channels such that the toxin does not readily bind other targets (see Ion Channel toxins ). As such, neurotoxins provide an effective means by which certain elements of the nervous system may be accurately and efficiently targeted. An early example of neurotoxin based targeting used radiolabeled tetrodotoxin to assay sodium channels and obtain precise measurements about their concentration along nerve membranes . Likewise through isolation of certain channel activities, neurotoxins have provided

2976-679: A prominent adaxial groove. Stipules are lacking. The expanding leaves are conduplicate, green, covered with rusty tomentum beneath, and hairy above; when fully grown they are smooth, dark green above, and paler beneath. When bruised, the leaves have a disagreeable odor similar to a green bell pepper . In autumn, the leaves are a rusty yellow, allowing pawpaw groves to be spotted from a long distance. Pawpaw flowers are perfect and protogynous , about 1–2 in (3–5 cm) across, rich red-purple or maroon when mature, with three sepals and six petals. They are borne singly on stout, hairy, axillary peduncles . The flowers are produced in early spring at

3100-453: A result of early lead exposure. In addition to inducing apoptosis, lead inhibits interneuron signaling through the disruption of calcium-mediated neurotransmitter release. As a neurotoxin, ethanol has been shown to induce nervous system damage and affect the body in a variety of ways. Among the known effects of ethanol exposure are both transient and lasting consequences. Some of the lasting effects include long-term reduced neurogenesis in

3224-438: A result of increased generation of reactive oxidative species (ROS). This is a plausible mechanism, as there is a reduced presence in the fetal brain of antioxidant enzymes such as catalase and peroxidase . In support of this mechanism, administration of high levels of dietary vitamin E results in reduced or eliminated ethanol-induced neurotoxic effects in fetuses. n- Hexane is a neurotoxin which has been responsible for

3348-641: A tiny portion of Kalamazoo County . Tributaries of the main branch include: North branch tributaries include: The north branch headwaters arise in springs near the Wolf Lake State Fish Hatchery. South branch tributaries include: The south branch headwaters arise in Decatur Township in eastern Van Buren County. Asimina triloba Asimina triloba , the American papaw , pawpaw , paw paw , or paw-paw , among many regional names,

3472-405: A week if refrigerated. This short shelf-life and difficulty shipping whole are a primary barrier to the success of pawpaw as a commercial fruit. The easily-bruised pawpaw fruits do not ship well unless frozen. Where pawpaws grow, the fruit pulp is also used locally in baked dessert recipes, with pawpaw substituted with volumetric equivalency in many banana-based recipes. The sweet and creamy fruit

3596-590: Is Carica papaya . By 1598, English-speaking people in the Caribbean were calling these plants "pawpaws" or "papaws" ... [yet later, when English-speakers settled in] the temperate Americas, they found another tree with a similarly aromatic, sweet fruit. It reminded them of the "papaya", which had already become "papaw", so that is what they called these different plants ... By 1760, the names "papaw" and "pawpaw" were being applied to A. triloba . Yet A. triloba has had numerous local common names, many of which compare it to

3720-578: Is a patch-forming (clonal) understory tree of hardwood forests, which is found in well-drained, deep, fertile bottomland and also hilly upland habitat. It has large, simple leaves with drip tips, more characteristic of plants in tropical rainforests than within this species' temperate range. Pawpaw fruits are the largest edible fruit indigenous to the United States (not counting squashes , which are typically considered vegetables rather than fruit for culinary purposes, although in botany they are classified as fruit). Pawpaw fruits are sweet, with

3844-518: Is a common feature of some plants native to the Western Hemisphere, where a large proportion of megafauna went extinct near the end of the glacial episodes. Such fruits are now regarded as evolutionary anachronisms . Their anatomical features, such as seeds too big for today's fruit eaters to swallow and then defecate, means they are no longer well adapted for current ecological conditions. Another indicator of dispersal adaptation for megafauna

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3968-432: Is a coolwater stream as evidenced by the presence of burbot and mottled sculpin, it also contains hornyhead chub, common shiner, johnny darter, and walleye. Several riparian wetlands provide excellent habitat for northern pike. The fish community near the mouth is influenced by its proximity to Lake Michigan, and steelhead trout ( Oncorhynchus mykiss ) are stocked there. Potamodromous trout and salmon have access to most of

4092-458: Is a member of the Annonaceae family, commonly referred to as the "custard-apple" or "soursop" family. Annonaceae are a diverse group comprising the single largest family of the order Magnoliales . They are a tropical family consisting of 112 accepted genera with about 2,200 species spread primarily across South America, Africa, and Southeast Asia. The pawpaw is an exception to this pattern, as it

4216-610: Is a neurotoxin commonly found concentrated in areas exposed to agricultural runoff , mining , and smelting sites (Martinez-Finley 2011). One of the effects of arsenic ingestion during the development of the nervous system is the inhibition of neurite growth which can occur both in PNS and the CNS. This neurite growth inhibition can often lead to defects in neural migration , and significant morphological changes of neurons during development , ) often leading to neural tube defects in neonates . As

4340-428: Is a new nonpeptide amino acid toxin that stimulate the glutamate receptors in neurons. Caramboxin is an agonist of both NMDA and AMPA glutamatergic ionotropic receptors with potent excitatory, convulsant, and neurodegenerative properties. The term " curare " is ambiguous because it has been used to describe a number of poisons which at the time of naming were understood differently from present day understandings. In

4464-411: Is a particularly useful molecule for investigating acetylcholine receptors in the nervous system. The deadliness of the toxin means that it has a high military potential as a toxin weapon. Bungarotoxin is a compound with known interaction with nicotinic acetylcholine receptors (nAChRs), which constitute a family of ion channels whose activity is triggered by neurotransmitter binding. Bungarotoxin

4588-471: Is a poison produced by organisms belonging to the Tetraodontiformes order , which includes the puffer fish , ocean sunfish , and porcupine fish . Within the puffer fish, TTX is found in the liver , gonads , intestines , and skin . TTX can be fatal if consumed, and has become a common form of poisoning in many countries. Common symptoms of TTX consumption include paraesthesia (often restricted to

4712-431: Is a potent neurotoxin whose toxicity has been recognized for at least thousands of years. Though neurotoxic effects for lead are found in both adults and young children , the developing brain is particularly susceptible to lead-induced harm, effects which can include apoptosis and excitotoxicity. An underlying mechanism by which lead is able to cause harm is its ability to be transported by calcium ATPase pumps across

4836-482: Is a small deciduous tree native to the eastern United States and southern Ontario , Canada, producing a large, yellowish-green to brown fruit . Asimina is the only temperate genus in the tropical and subtropical flowering plant family Annonaceae , and Asimina triloba has the most northern range of all. Well-known tropical fruits of different genera in family Annonaceae include the custard-apple , cherimoya , sweetsop , ylang-ylang , and soursop . The pawpaw

4960-453: Is based on its importance in glutamate excitotoxicity, as NO is generated in a calcium-dependent manner in response to glutamate mediated NMDA activation, which occurs at an elevated rate in glutamate excitotoxicity. Though NO facilitates increased blood flow to potentially ischemic regions of the brain, it is also capable of increasing oxidative stress , inducing DNA damage and apoptosis. Thus an increased presence of NO in an ischemic area of

5084-471: Is common. Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant and antitoxin administration. Exposure to neurotoxins in society is not new, as civilizations have been exposed to neurologically destructive compounds for thousands of years. One notable example is the possible significant lead exposure during the Roman Empire resulting from

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5208-656: Is commonly mixed into ice cream or blended into pancakes and other breads. Neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity ). Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components

5332-472: Is important in the study of nervous systems. Common examples of neurotoxins include lead , ethanol (drinking alcohol), glutamate , nitric oxide , botulinum toxin (e.g. Botox), tetanus toxin , and tetrodotoxin . Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations. Neurotoxins inhibit neuron control over ion concentrations across

5456-483: Is its destructive nature towards the cytoskeleton through inhibition of neurofilament transport. This is particularly destructive as neurofilaments are used in basic cell structure and support. Lithium administration has shown promise, however, in restoring some of the lost neurofilament motility. Additionally, similar to other neurotoxin treatments, the administration of certain antioxidants has shown some promise in reducing neurotoxicity of ingested arsenic. Lead

5580-400: Is often seen through two routes of administration, either through consumption or through endogenous ailments such as liver failure . One notable case in which ammonia toxicity is common is in response to cirrhosis of the liver which results in hepatic encephalopathy , and can result in cerebral edema (Haussinger 2006). This cerebral edema can be the result of nervous cell remodeling. As

5704-470: Is one of several features that signify a "beetle pollination syndrome ". Other floral features of pawpaw indicative of beetle pollination include petals that curve over the downward-pointing flower center, along with food-rich fleshy bases of the inner whorl of petals. A "pollination chamber" is thereby created at a depth that only small beetles can access during the initial female-receptive stage of floral bloom. As with other well-studied species of Annonaceae,

5828-532: Is particularly specific for α7-nAChR . This α7-nAChR functions to allow calcium ion influx into cells, and thus when blocked by ingested bungarotoxin will produce damaging effects, as ACh signaling will be inhibited. Likewise, the use of α-bungarotoxin can be very useful in neuroscience if it is desirable to block calcium flux in order to isolate effects of other channels. Additionally, different forms of bungarotoxin may be useful for studying inhibited nAChRs and their resultant calcium ion flow in different systems of

5952-494: Is produced in a number of different forms, though one of the commonly used forms is the long chain alpha form, α-bungarotoxin , which is isolated from the banded krait snake . Though extremely toxic if ingested, α-bungarotoxin has shown extensive usefulness in neuroscience as it is particularly adept at isolating nAChRs due to its high affinity to the receptors. As there are multiple forms of bungarotoxin, there are different forms of nAChRs to which they will bind, and α-bungarotoxin

6076-697: Is smaller than pawpaw in both its flower and its woody growth. A. parviflora is more shrublike, rarely growing even a third as tall as pawpaw. Genomically verified hybrids of A. triloba and A. parviflora have been classified as Asimina piedmontana . Pawpaw are self-incompatible , meaning pollen cannot fertilize flowers on the same plant. This, coupled with the pawpaw's tendency to form clonal patches can reduce fertilization success. A single patch consisting of many stems may therefore produce no fruit if all stems are genetically identical. Fruitless pawpaw patches have been documented in Ohio. The floral scent of Asimina triloba has been described as "yeasty", which

6200-435: Is that pawpaw fruit (wild types and most cultivars) tend to remain green or become blotched with brown when at peak ripeness. Mammals (other than primates ) rely on olfactory rather than visual clues for discerning ripe fruit, so fruit color is no signal of ripeness for large mammals. An advantage of maintaining green fruit skin throughout the ripening process is that photosynthesis can continue during this time. Following

6324-822: Is the ability for ethanol to inhibit NMDA receptors in the hippocampus, resulting in reduced long-term potentiation (LTP) and memory acquisition. NMDA has been shown to play an important role in LTP and consequently memory formation. With chronic ethanol intake, however, the susceptibility of these NMDA receptors to induce LTP increases in the mesolimbic dopamine neurons in an inositol 1,4,5-triphosphate (IP3) dependent manner. This reorganization may lead to neuronal cytotoxicity both through hyperactivation of postsynaptic neurons and through induced addiction to continuous ethanol consumption. It has, additionally, been shown that ethanol directly reduces intracellular calcium ion accumulation through inhibited NMDA receptor activity, and thus reduces

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6448-685: Is the dark maroon color of the petals. Hence, while no scholarly papers have documented carrion or dung flies as effective pollinators in field observations, the strength of this hypothesis has led to placement of carrion during the bloom time in pawpaw orchards by some horticultural growers. Professional papers on genus Asimina and its species have warned of the difficulties in discerning whether insects observed on or collected from flowers are effective pollinators or merely casual and thus opportunistic visitors. A citizen science project in southern Michigan utilized natural history forms of observation, along with video and photo documentation, during

6572-506: Is the most temperate member of its family. Its range extends as far north as the southern portion of Ontario, Canada . Within the United States, pawpaw is native to the eastern, southern, and midwestern states, ranging from New York westward to southeastern Nebraska , southward to eastern Texas and the panhandle of Florida . The tree is commonly found in the wild within or along the slopes of floodplains and shady, rich bottomlands, but it requires somewhat elevated slopes because it has

6696-405: Is this capability to inhibit potassium flux in neurons that has made TEA one of the most important tools in neuroscience. It has been hypothesized that the ability for TEA to inhibit potassium channels is derived from its similar space-filling structure to potassium ions. What makes TEA very useful for neuroscientists is its specific ability to eliminate potassium channel activity, thereby allowing

6820-536: Is usually associated is muscle paralysis and resultant death. Curare notably functions to inhibit nicotinic acetylcholine receptors at the neuromuscular junction . Normally, these receptor channels allow sodium ions into muscle cells to initiate an action potential that leads to muscle contraction. By blocking the receptors, the neurotoxin is capable of significantly reducing neuromuscular junction signaling, an effect which has resulted in its use by anesthesiologists to produce muscular relaxation. Ammonia toxicity

6944-500: Is working on restoring pawpaw for the purpose of encouraging return of the zebra swallowtail as well as the general restoration of riparian areas. In June 2024 a zebra swallowtail was documented laying eggs on a backyard pawpaw plant in Pittsburgh. This was the first time that this butterfly species was seen there since industrialization and river slope destruction had decimated its plant host. A local news editorial wrote, "The return of

7068-544: The Magnoliids (of which Annonaceae is the most species-rich taxonomic family). Beetles are the dominant form of pollinator ascribed for genera and species within the Annonaceae family. However, two species of genus Asimina ( Asimina triloba and Asimina parviflora ) bear a floral character that has given rise to an alternative hypothesis that carrion or dung flies are their effective pollinators. That floral characteristic

7192-571: The TRPV1 receptor expressed on cholinergic neurons and inhibit the toxic effects of BTX. Tetanus neurotoxin (TeNT) is a compound that functionally reduces inhibitory transmissions in the nervous system resulting in muscular tetany. TeNT is similar to BTX, and is in fact highly similar in structure and origin; both belonging to the same category of clostridial neurotoxins . Like BTX, TeNT inhibits inter-neuron communication by means of vesicular neurotransmitter (NT) release. One notable difference between

7316-521: The cell membrane, or communication between neurons across a synapse . Local pathology of neurotoxin exposure often includes neuron excitotoxicity or apoptosis but can also include glial cell damage. Macroscopic manifestations of neurotoxin exposure can include widespread central nervous system damage such as intellectual disability , persistent memory impairments, epilepsy , and dementia . Additionally, neurotoxin-mediated peripheral nervous system damage such as neuropathy or myopathy

7440-906: The extinction of much of the ice age megafauna, bears would have continued dispersing pawpaw seeds in their dung. Hand carrying of fruit and seeds by humans expanding from Asia into North America would have extended the range of long-distance seed dispersal. Humans intentionally continue this role today via horticultural plantings, along with wild plantings as far north as Massachusetts, Pennsylvania, and Michigan. Small mammals , including raccoons , gray foxes , opossums , and squirrels , assist in local movements of seeds. Pawpaw defends against herbivory by producing strong-smelling natural toxins known as acetogenins . Pawpaw leaves, twigs, and bark are therefore seldom consumed by rabbits , deer , or goats, nor by insects. However, mules have been seen eating pawpaw leaves in Maryland . Larvae of

7564-539: The hippocampus , widespread brain atrophy, and induced inflammation in the brain. Of note, chronic ethanol ingestion has additionally been shown to induce reorganization of cellular membrane constituents, leading to a lipid bilayer marked by increased membrane concentrations of cholesterol and saturated fat . This is important as neurotransmitter transport can be impaired through vesicular transport inhibition, resulting in diminished neural network function. One significant example of reduced inter-neuron communication

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7688-436: The mouth and limbs ), muscle weakness, nausea , and vomiting and often manifest within 30 minutes of ingestion . The primary mechanism by which TTX is toxic is through the inhibition of sodium channel function, which reduces the functional capacity of neuron communication. This inhibition largely affects a susceptible subset of sodium channels known as TTX-sensitive (TTX-s), which also happens to be largely responsible for

7812-632: The spotted turtle . In November 2003, The Nature Conservancy announced the purchase of 139 acres (0.6 km) in the Paw Paw Prairie Fen , located in the East Branch of the river near Mattawan. The Sarett Nature Center owns 800 acres (3.2 km) of along the river in Berrien County, just north of Benton Harbor. The Paw Paw River has 39 species of fish including walleye , bass , bluegill , black crappie , and northern pike . The mainstem

7936-518: The zebra swallowtail ( Eurytides marcellus ), a butterfly , feed exclusively on young leaves of A. triloba and various other pawpaw ( Asimina ) species, but do not occur in great numbers on the plants. Chemicals consumed by the caterpillars confer protection throughout the butterflies' lives, as trace amounts of acetogenins remain present, making them unpalatable to birds and other predators. A partially citizen-led project in Pittsburgh, Pennsylvania

8060-439: The BBB, allowing for direct contact with the fragile cells within the central nervous system. Neurotoxicity results from lead's ability to act in a similar manner to calcium ions, as concentrated lead will lead to cellular uptake of calcium which disrupts cellular homeostasis and induces apoptosis. It is this intracellular calcium increase that activates protein kinase C (PKC), which manifests as learning deficits in children as

8184-637: The BBB. To even further complicate the process of determining neurotoxins when testing in-vitro, neurotoxicity and cytotoxicity may be difficult to distinguish as exposing neurons directly to compounds may not be possible in-vivo, as it is in-vitro. Additionally, the response of cells to chemicals may not accurately convey a distinction between neurotoxins and cytotoxins, as symptoms like oxidative stress or skeletal modifications may occur in response to either. In an effort to address this complication, neurite outgrowths (either axonal or dendritic) in response to applied compounds have recently been proposed as

8308-448: The CNS can produce significantly toxic effects. Glutamate , like nitric oxide, is an endogenously produced compound used by neurons to perform normally, being present in small concentrations throughout the gray matter of the CNS. One of the most notable uses of endogenous glutamate is its functionality as an excitatory neurotransmitter. When concentrated, however, glutamate becomes toxic to surrounding neurons. This toxicity can be both

8432-656: The Spanish papaya , an American tropical and subtropical fruit ( Carica papaya ) sometimes also called "papaw", perhaps because of the superficial similarity of their fruits and the fact that both have very large leaves. The name pawpaw or papaw, first recorded in print in English in 1598, originally meant the giant herb Carica papaya or its fruit (as it still commonly does in many English-speaking communities, including Australia, New Zealand, and South Africa). Daniel F. Austin's Florida Ethnobotany states that: The original "papaw" ...

8556-477: The ability to improve the original Hodgkin-Huxley model of the neuron in which it was theorized that single generic sodium and potassium channels could account for most nervous tissue function. From this basic understanding, the use of common compounds such as tetrodotoxin, tetraethylammonium , and bungarotoxins have led to a much deeper understanding of the distinct ways in which individual neurons may behave. As neurotoxins are compounds which adversely affect

8680-449: The blood, such as those experiencing renal failure . Patients experiencing aluminium toxicity can exhibit symptoms such as impaired learning and reduced motor coordination . Additionally, systemic aluminium levels are known to increase with age, and have been shown to correlate with Alzheimer's disease , implicating it as a neurotoxic causative compound of the disease. Despite its known toxicity in its ionic form, studies are divided on

8804-432: The body in useful and healthy ways, such as nitric oxide which is used in cell communication. It is often only when these endogenous compounds become highly concentrated that they lead to dangerous effects. Though nitric oxide (NO) is commonly used by the nervous system in inter-neuron communication and signaling, it can be active in mechanisms leading to ischemia in the cerebrum (Iadecola 1998). The neurotoxicity of NO

8928-444: The body. For example, α-bungarotoxin is specific for nAChRs found in the musculature and κ-bungarotoxin is specific for nAChRs found in neurons. Caramboxin (CBX) is a toxin found in star fruit ( Averrhoa carambola) . Individuals with some types of kidney disease are susceptible to adverse neurological effects including intoxication, seizures and even death after eating star fruit or drinking juice made of this fruit. Caramboxin

9052-485: The brain , which through the function of their ependymal cells, are responsible for the synthesis of cerebrospinal fluid (CSF). Importantly, through selective passage of ions and nutrients and trapping heavy metals such as lead, the choroid plexuses maintain a strictly regulated environment which contains the brain and spinal cord. By being hydrophobic and small, or inhibiting astrocyte function, some compounds including certain neurotoxins are able to penetrate into

9176-427: The brain and induce significant damage. In modern times, scientists and physicians have been presented with the challenge of identifying and treating neurotoxins, which has resulted in a growing interest in both neurotoxicology research and clinical studies. Though clinical neurotoxicology is largely a burgeoning field, extensive inroads have been made in the identification of many environmental neurotoxins leading to

9300-419: The brain and inhibit some of the crucial functions of the blood brain barrier (BBB). A loss of function in the BBB can produce significant damage to the neurons in the CNS, as the barrier protecting the brain from other toxins found in the blood will no longer be capable of such action. Though the metal is known to be neurotoxic, effects are usually restricted to patients incapable of removing excess ions from

9424-412: The brain requires nutrient entry and waste removal, it is perfused by blood flow. Blood can carry a number of ingested toxins, however, which would induce significant neuron death if they reach nervous tissue. Thus, protective cells termed astrocytes surround the capillaries in the brain and absorb nutrients from the blood and subsequently transport them to the neurons, effectively isolating the brain from

9548-549: The brain such as vitamin E . As the fetal brain is relatively fragile and susceptible to induced stresses, severe deleterious effects of alcohol exposure can be seen in important areas such as the hippocampus and cerebellum . The severity of these effects is directly dependent upon the amount and frequency of ethanol consumption by the mother, and the stage in development of the fetus. It is known that ethanol exposure results in reduced antioxidant levels, mitochondrial dysfunction (Chu 2007), and subsequent neuronal death, seemingly as

9672-693: The capacity for the occurrence of LTP. In addition to the neurotoxic effects of ethanol in mature organisms, chronic ingestion is capable of inducing severe developmental defects. Evidence was first shown in 1973 of a connection between chronic ethanol intake by mothers and defects in their offspring. This work was responsible for creating the classification of fetal alcohol syndrome , a disease characterized by common morphogenesis aberrations such as defects in craniofacial formation, limb development, and cardiovascular formation. The magnitude of ethanol neurotoxicity in fetuses leading to fetal alcohol syndrome has been shown to be dependent on antioxidant levels in

9796-507: The case of botulinum toxin , or even nervous tissue death. The time required for the onset of symptoms upon neurotoxin exposure can vary between different toxins, being on the order of hours for botulinum toxin and years for lead. Tetanus toxin Mercury Curare Caramboxin , 25I-NBOMe , JWH-018 , 5-MEO-DiPT Arsenic N-Hexane , Methanol Glutamate , Dopamine Tetrodotoxin (TTX)

9920-629: The citizen project on the ground-level side of rotting fruit in a pawpaw orchard in Michigan following the fruit harvest. Until the expansion of humans into North America at the end of the Pleistocene , dispersal of pawpaw seeds would primarily have occurred via the dung of certain megafauna (such as mastodons , mammoths , and giant ground sloths ). The fruit of pawpaw is thus recognized as having coevolved with large mammals serving as long-distance seed dispersers. The megafaunal dispersal syndrome

10044-514: The classification of 750 to 1000 known potentially neurotoxic compounds. Due to the critical importance of finding neurotoxins in common environments, specific protocols have been developed by the United States Environmental Protection Agency (EPA) for testing and determining neurotoxic effects of compounds (USEPA 1998). Additionally, in vitro systems have increased in use as they provide significant improvements over

10168-438: The conductance of chloride channels . Ingestion of lethal volumes of Cltx results in paralysis through this ion channel disruption. Similar to botulinum toxin, Cltx has been shown to possess significant therapeutic value. Evidence has shown that Cltx can inhibit the ability for gliomas to infiltrate healthy nervous tissue in the brain, significantly reducing the potential invasive harm caused by tumors. Conotoxins represent

10292-466: The deaths of cows that drank from a lake containing an algal bloom in Saskatchewan, Canada. It is a cyanotoxin produced by at least four different genera of cyanobacteria , and has been reported in North America, Europe, Africa, Asia, and New Zealand. Toxic effects from anatoxin- a progress very rapidly because it acts directly on the nerve cells ( neurons ). The progressive symptoms of anatoxin-

10416-480: The deer avoid them but consume seedlings of most other woody plants . The genus Asimina exists on only one continent, North America. This gives the pawpaw a distinct advantage in the modern world of transcontinental commerce. In contrast to North American tree genera whose ranges extend into Europe or Asia (notably, chestnut and elm ), global horticultural trade is therefore unlikely to introduce diseases that could decimate pawpaw. As for native disease,

10540-431: The delay in the shift from female to male floral stage offers beetles a secure, and possibly thermogenic , residence in which not only to feed but also to mate. Receptive stigmas at their arrival, followed by pollen-shedding stamens during pollinator departure, are regarded as an early form of mutualism evolved between plants and insects that is still dominant in the most ancient lineages of flowering plants, including

10664-498: The development of extensive plumbing networks and the habit of boiling vinegared wine in lead pans to sweeten it, the process generating lead acetate, known as "sugar of lead". In part, neurotoxins have been part of human history because of the fragile and susceptible nature of the nervous system, making it highly prone to disruption. The nervous tissue found in the brain , spinal cord , and periphery comprises an extraordinarily complex biological system that largely defines many of

10788-401: The disruption or destruction of necessary components within the nervous system . Neurotoxins, however, by their very design can be very useful in the field of neuroscience . As the nervous system in most organisms is both highly complex and necessary for survival, it has naturally become a target for attack by both predators and prey. As venomous organisms often use their neurotoxins to subdue

10912-399: The eastern United States, where large predators are almost entirely lacking, pawpaw is one of the few native subcanopy trees whose bark and leaves are too poisonous for deer to browse. It is therefore a viable species for forest understory restoration in areas where fragmented landscapes, dwellings, and parks status preclude hunting as a population control. The tough, fibrous inner bark of

11036-439: The emerging plants are not protected from direct sunlight. Patch-forming clonal growth is achieved by way of shallow, horizontally spreading stems ( rhizomes ). By retaining these interconnections, photosynthates can be shared among the stems ( ramets ). Stems that access sunlight can grow as tall as 30 feet and will bear the most fruit. Stems that develop under canopy shade tend to curve and bend in quest of sunlight patches, with

11160-455: The function of motor nerves and thus the contraction of the musculature in a manner similar to that of curare. Additionally, through chronic TEA administration, muscular atrophy would be induced. It was later determined that TEA functions in-vivo primarily through its ability to inhibit both the potassium channels responsible for the delayed rectifier seen in an action potential and some population of calcium-dependent potassium channels. It

11284-449: The inhibition of acetylcholinesterase capacity of organophosphates (includes parathion and sarin gas). Though methods of determining neurotoxicity still require significant development, the identification of deleterious compounds and toxin exposure symptoms has undergone significant improvement. Though diverse in chemical properties and functions, neurotoxins share the common property that they act by some mechanism leading to either

11408-563: The leaves, twigs, and bark of pawpaw trees can be used to make an organic insecticide . The earliest documented mention of pawpaws is in the 1541 report of the Spanish de Soto expedition, who found Native Americans east of the Mississippi River cultivating what some have identified as the pawpaw. The tree's scientific name ( Asimina triloba ) comes from the Powhatan word Assimina, which

11532-463: The membranes of neurons but not those of muscle cells. Botulinum toxin (BTX) is a group of neurotoxins consisting of eight distinct compounds, referred to as BTX-A,B,C,D,E,F,G,H, which are produced by the bacterium Clostridium botulinum and lead to muscular paralysis . A notably unique feature of BTX is its relatively common therapeutic use in treating dystonia and spasticity disorders, as well as in inducing muscular atrophy despite being

11656-399: The more common in vivo systems of the past. Examples of improvements include tractable, uniform environments, and the elimination of contaminating effects of systemic metabolism. In vitro systems, however, have presented problems as it has been difficult to properly replicate the complexities of the nervous system, such as the interactions between supporting astrocytes and neurons in creating

11780-632: The most poisonous substance known. BTX functions peripherally to inhibit acetylcholine (ACh) release at the neuromuscular junction through degradation of the SNARE proteins required for ACh vesicle-membrane fusion . As the toxin is highly biologically active, an estimated dose of 1μg/kg body weight is sufficient to induce an insufficient tidal volume and resultant death by asphyxiation . Due to its high toxicity, BTX antitoxins have been an active area of research. It has been shown that capsaicin (active compound responsible for heat in chili peppers ) can bind

11904-411: The most potent neurotoxins ever discovered. MeHg is usually acquired through consumption of seafood , as it tends to concentrate in organisms high on the food chain. It is known that the mercuric ion inhibits amino acid (AA) and glutamate (Glu) transport, potentially leading to excitotoxic effects. Investigations into anatoxin- a , also known as "Very Fast Death Factor", began in 1961 following

12028-408: The muscarinic acetylcholine antagonist atropine (which will inhibit parasympathetic activity), however, can increase sympathetic nerve activity enough to improve the chance of survival after TTX exposure. Tetraethylammonium (TEA) is a compound that, like a number of neurotoxins, was first identified through its damaging effects to the nervous system and shown to have the capacity of inhibiting

12152-425: The nervous system, a number of mechanisms through which they function are through the inhibition of neuron cellular processes. These inhibited processes can range from membrane depolarization mechanisms to inter-neuron communication . By inhibiting the ability for neurons to perform their expected intracellular functions, or pass a signal to a neighboring cell, neurotoxins can induce systemic nervous system arrest as in

12276-515: The past the characterization has meant poisons used by South American tribes on arrows or darts , though it has matured to specify a specific categorization of poisons which act on the neuromuscular junction to inhibit signaling and thus induce muscle relaxation. The neurotoxin category contains a number of distinct poisons, though all were originally purified from plants originating in South America. The effect with which injected curare poison

12400-551: The pawpaw fares very well. There are no known disease agents (including insects) that are especially damaging. Consequently, planting of pawpaw for landscaping or fruit production requires little to no attention to disease management. Pawpaws are sometimes included in ecological restoration plantings , as they have many characteristics that make them ideal for repair of riparian ecosystems. The tree's fondness of wet soil and tendency to multiply clonally to form dense and well-rooted thickets can protect against erosion and runoff. As

12524-459: The pawpaw has traditionally been used by Native Americans and settlers in the Midwest for making ropes , fishing nets , and mats , and for stringing fish. Because the exotic emerald ash borer beetle is destroying black ash trees ( Fraxinus nigra ) in its native range, a basketmaker in Michigan whose ancestors traditionally used this northern species of ash has begun planting pawpaw seeds as

12648-458: The pawpaw peduncle borer, whose larvae can be found in flowers, and Omphalocera munroei , the asimina webworm, whose larvae mostly feed upon leaves. Pawpaw is well suited to life as an understory tree. Its large seed enables significant below-ground growth before the above-ground growth needs to access sunlight for photosynthesis. As well, the species is so shade-adapted that propagation of seedlings in nursery and landscape settings may fail if

12772-405: The pawpaw such as riwahárikstikuc ( Pawnee ), tózhaⁿ hu ( Kansa ), and umbi ( Choctaw ). A. triloba is a large shrub or small tree growing to a height of 35 ft (11 m), rarely as tall as 45 ft (14 m), with trunks 8–12 in (20–30 cm) or more in diameter. The large leaves of pawpaw trees are clustered symmetrically at the ends of the branches, giving

12896-401: The persistence of neurons through an individual's lifetime, leading to compounding of damages. As a result, the nervous system has a number of mechanisms designed to protect it from internal and external assaults, including the blood brain barrier. The blood–brain barrier (BBB) is one critical example of protection which prevents toxins and other adverse compounds from reaching the brain. As

13020-570: The point of obscurity in favor of other commercial fruits. Despite its very short shelf life, vulnerability to bruising, and inability to fully ripen if harvested early, pawpaw has developed a specialty market appeal in some regions of its native range, including southern Ontario . As described by horticulturist Barbara Damrosch, the fruit of the pawpaw "looks a bit like mango, but with pale yellow, custardy, spoonable flesh and black, easy-to-remove seeds." Wild-collected pawpaw fruits ripen in late August to mid-September through most of their range, but

13144-454: The poisoning of several workers in Chinese electronics factories in recent years. MPP , the toxic metabolite of MPTP is a selective neurotoxin which interferes with oxidative phosphorylation in mitochondria by inhibiting complex I , leading to the depletion of ATP and subsequent cell death. This occurs almost exclusively in dopaminergic neurons of the substantia nigra , resulting in

13268-399: The potential toxicity of using aluminium in packaging and cooking appliances. Mercury is capable of inducing CNS damage by migrating into the brain by crossing the BBB. Mercury exists in a number of different compounds, though methylmercury (MeHg ), dimethylmercury and diethylmercury are the only significantly neurotoxic forms. Diethylmercury and dimethylmercury are considered some of

13392-419: The presentation of permanent parkinsonism in exposed subjects 2–3 days after administration. Unlike most common sources of neurotoxins which are acquired by the body through ingestion, endogenous neurotoxins both originate from and exert their effects in-vivo . Additionally, though most venoms and exogenous neurotoxins will rarely possess useful in-vivo capabilities, endogenous neurotoxins are commonly used by

13516-399: The receptor, acetylcholine . Once it has triggered a contraction, anatoxin- a does not allow the neurons to return to their resting state, because it is not degraded by cholinesterase which normally performs this function. As a result, the muscle cells contract permanently, the communication between the brain and the muscles is disrupted and breathing stops. When it was first discovered,

13640-413: The relish of most people." Ohio botanist William B. Werthner wrote, "The fruit ... has a tangy wild-wood flavor peculiarly its own. It is sweet, yet rather cloying to the taste and a wee bit puckery – only a boy can eat more than one at a time." Fresh fruits of the pawpaw are commonly eaten raw, either chilled or at room temperature. However, they can be kept only 2–3 days at room temperature, or about

13764-458: The river system, and are shore-fished in the fall upstream of Hartford . There are 24 registered dams within the Paw Paw River sub-watershed, but these dams are all low head dams or on small tributaries, so potamodromous trout and salmon can migrate into its headwaters at Campbell Creek. The watershed covers about 445 square miles (1,150 km), mostly in Van Buren County, and also drains

13888-527: The root terms rassi= "divided lengthwise into equal parts" and min= "seed, fruit, nut, berry, etc." through the French colonial asiminier . The specific epithet triloba in the species' scientific name refers to its lobed fruits (three lobes, "fructibus trifidus," in Linnaeus' original description). The common name of this species is variously spelled pawpaw, paw paw, paw-paw, and papaw. It probably derives from

14012-399: The same time as or slightly before the new leaves appear, and have a faint fetid or yeasty smell. The fruit of the pawpaw is a large, yellowish-green to brown berry , 2–6 in (5–15 cm) long and 1–3 in (3–8 cm) broad, weighing from 0.7–18 oz (20–510 g), containing several brown or black seeds 1 ⁄ 2 –1 in (15–25 mm) in diameter embedded in

14136-539: The sodium current that drives the depolarization phase of neuron action potentials . TTX-resistant (TTX-r) is another form of sodium channel which has limited sensitivity to TTX, and is largely found in small diameter axons such as those found in nociception neurons . When a significant level of TTX is ingested, it will bind sodium channels on neurons and reduce their membrane permeability to sodium. This results in an increased effective threshold of required excitatory signals in order to induce an action potential in

14260-462: The soft, edible fruit pulp. The conspicuous fruits begin developing after the plants flower; they are initially green, maturing by September or October to green, yellowish green, or brown. When mature, the heavy fruits bend the weak branches down. Full ripening often happens only after the fruit falls naturally, thus signifying a seed dispersal strategy aimed at ground-based, rather than arboreal , mammals. Other characteristics: Asimina triloba

14384-476: The species is found only in portions of southern Ontario , it has a rank of N3 (vulnerable), and a NatureServe subnational conservation rank of S3 (vulnerable) in Ontario. The Ontario Ministry of Natural Resources has given the species a general status of "Sensitive", and its populations there are monitored. In areas in which deer populations are dense, pawpaws appear to be becoming more abundant locally, since

14508-401: The spinal cord after entering through endocytosis . This results in a loss of function in inhibitory neurons within the CNS resulting in systemic muscular contractions . Similar to the prognosis of a lethal dose of BTX, TeNT leads to paralysis and subsequent suffocation . Neurotoxic behavior of Aluminium is known to occur upon entry into the circulatory system , where it can migrate to

14632-432: The study of neuron response contributions of other ion channels such as voltage gated sodium channels. In addition to its many uses in neuroscience research, TEA has been shown to perform as an effective treatment of Parkinson's disease through its ability to limit the progression of the disease. Chlorotoxin (Cltx) is the active compound found in scorpion venom, and is primarily toxic because of its ability to inhibit

14756-499: The toxic effects of ammonia on astrocyte remodeling can be reduced through administration of L-carnitine . This astrocyte remodeling appears to be mediated through ammonia-induced mitochondrial permeability transition. This mitochondrial transition is a direct result of glutamine activity a compound which forms from ammonia in-vivo. Administration of antioxidants or glutaminase inhibitor can reduce this mitochondrial transition, and potentially also astrocyte remodeling. Arsenic

14880-539: The toxin was called the Very Fast Death Factor (VFDF) because when it was injected into the body cavity of mice it induced tremors, paralysis and death within a few minutes. In 1977, the structure of VFDF was determined as a secondary, bicyclic amine alkaloid , and it was renamed anatoxin- a . Structurally, it is similar to cocaine. There is continued interest in anatoxin- a because of the dangers it presents to recreational and drinking waters, and because it

15004-422: The two compounds is that while BTX inhibits muscular contractions , TeNT induces them. Though both toxins inhibit vesicle release at neuron synapses, the reason for this different manifestation is that BTX functions mainly in the peripheral nervous system (PNS) while TeNT is largely active in the central nervous system (CNS). This is a result of TeNT migration through motor neurons to the inhibitory neurons of

15128-407: The unique forms of conotoxins, ω-conotoxin ( ω-CgTx ) is highly specific for Ca channels and has shown usefulness in isolating them from a system. As calcium flux is necessary for proper excitability of a cell, any significant inhibition could prevent a large amount of functionality. Significantly, ω-CgTx is capable of long term binding to and inhibition of voltage-dependent calcium channels located in

15252-404: The unique traits of individuals. As with any highly complex system, however, even small perturbations to its environment can lead to significant functional disruptions. Properties leading to the susceptibility of nervous tissue include a high surface area of neurons, a high lipid content which retains lipophilic toxins, high blood flow to the brain inducing increased effective toxin exposure, and

15376-494: The zebra swallowtail, after 87 years, is a huge success for naturalists, conservationists and native tree lovers.... Organizations like Grow Pittsburgh, Tree Pittsburgh, the Pittsburgh Parks Conservancy and dedicated chat groups for Pittsburgh conservationists made the zebra swallowtail butterfly’s restoration possible." Other insects that have evolved the ability to consume pawpaws include Talponia plummeriana ,

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