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93-418: TETS is a neurotoxin and convulsant , causing lethal convulsions . Its effect is similar to but stronger than picrotoxin , a GABA-A receptor antagonist widely used in research. As one of the most hazardous pesticides, it is 100 times more toxic than potassium cyanide . TETS binds to neuronal GABA gated chloride channels , often causing status epilepticus . No antidote is known. The lethal dose for humans

186-562: A "fantasy" (game) that solely relies on the skill being mastered, rather than the other way around. These fantasies also tend to possess a few characteristics, such as (1) understanding that the fantasy and the skill that is being learned are inextricably linked, (2) the fantasy context and the instructional content being provided have an intrinsic and continuous link, and (3) endogenous fantasies tend to include more intellectually challenging and captivating content compared to exogenous fantasies. In materials science , an exogenous property of

279-423: 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

372-444: 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

465-433: 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

558-469: 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,

651-1172: A dose-dependent, non-competitive response to TETS that is reversible. Recent studies have indicated the usefulness of pH sensitivity in identifying Chloride ion influx, resulting from GABAA receptor excitation. Other potential screening tools include spontaneous Calcium ion oscillations seen in hippocampal cell cultures from new born mice. This phenomenon can be measured by Calcium ion sensitive fluorescent dye. Further analyses showed that these Calcium ion oscillations are sensitive to MK-801 (an NMDA open channel blocker), suggesting that NMDA receptor operated channels are involved in TMDT induced spontaneous activity. When considering GABAA receptor activity, diazepam and pregnanolone reversed TMDT activity when applied to cell cultures individually and in combination. MK-801 and ketamine show more antagonistic effects on TMDT than diazepam within cerebral cortical cell cultures of embryonic rats. Low dosages of ketamine and MK-801, administered separately, were associated with increased clonic seizures with no effect on tonic clonic seizures on mice exposed to TETS. Further analysis on

744-899: A factor that can depict economic forces as a whole. In economic sociology , Project IDEA (Interdisciplinary Dimensions of Economic Analysis) gave notion to understanding the exogenous factors that play a role within economic theory . Developed from the International Social Science Council (ISSC) in the year of 1982, Project IDEA was founded to gather ideas from economists and sociologists in order to conceptualize what economic sociology incorporates, as they have sought to understand why these two fields have been estranged from each other. Such exogenous factors in economic theory include laws placed in economic systems by governments, ranks of social classes in populations, and preferences based on social factors of an individual. In econometrics , an endogenous random variable

837-414: 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

930-495: A much greater amount than the human body can handle. On the opposite end, endogenous obesity refers to obesity caused by disorders or issues outside an imbalance of food intake itself, which include genetic disorders , interruption of thyroid functions, and other syndromic disorders. In relation to cancer, carcinogens are exogenous factors, in which these are made up of various factors (chemical, biological, physical), causing cancer after having entering through several routes of

1023-466: 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

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1116-400: 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

1209-603: 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

1302-467: A result of direct lethality of glutamate on neurons and a result of induced calcium flux into neurons leading to swelling and necrosis. Support has been shown for these mechanisms playing significant roles in diseases and complications such as Huntington's disease , epilepsy , and stroke . Exogenous In a variety of contexts, exogeny or exogeneity (from Greek ἔξω éxō  'outside' and -γένεια -géneia  'to produce')

1395-453: 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

1488-438: 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

1581-471: A substantial impact on the structure of the knowledge generated. Through the perspective of Piaget , learning was known as the individual's former structures accommodated to those imposed by its current environment. The individual's accommodation is directed by the environment, which provides the structures to which the individual must adapt. In attentional psychology , exogenous stimuli are external stimuli without conscious intention. An example of this

1674-407: A traditional regression model . An exogenous contrast agent , in medical imaging for example, is a liquid injected into the patient intravenously that enhances visibility of a pathology, such as a tumor . An exogenous factor is any material that is present and active in an individual organism or living cell but that originated outside that organism, as opposed to an endogenous factor. In

1767-432: Is correlated with the error term in the econometric model, while an exogenous variable is not. However, exogenous variables aid in the explanation of endogenous variable variances. In the preset group, it is typical to include historical values of endogenous variables. Exogenous variables are independent of the model's disturbance term , since they are preset. They meet the same conditions as explanatory variables do in

1860-563: Is 7–10 mg. Poisoning is diagnosed by GC-MS and the treatment is mainly supportive, with large IV doses of a benzodiazepine (e.g clonazepam ) and pyridoxine to control symptoms. TETS is sequestered in tissues of poisoned birds and can thus pose severe risk of secondary poisoning . Previous research has documented the effectiveness of tetramethylenedisulfotetramine against mice. The dangers of this chemical were first suspected in 1949. The U.S. Forest Service, looking to protect tree seeds for reforestation, noted its lethal effect against

1953-616: 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

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2046-428: 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

2139-411: 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

2232-479: 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

2325-431: 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

2418-505: Is attention drawn to a flashing light in the periphery of vision . In geography , exogenous processes all take place outside the Earth and all the other planets . Weathering , erosion , transportation and sedimentation are the main exogenous processes. Asides from climate, exogenous geographic factors are able to contribute to the overall process of distribution, including densities of populations and urbanizations of certain areas in

2511-453: 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

2604-477: 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

2697-472: 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

2790-483: 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

2883-399: Is noted to assume that knowledge comes from an individual's environment, which is assumed to be learned. Because an active individual is expected to be participating in the abstraction of knowledge from its environment, practical guidance of this result of participation remains the most crucial feature of directing the learning process. The structure of the individual's operating environment has

Tetramethylenedisulfotetramine - Misplaced Pages Continue

2976-400: 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

3069-532: 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

3162-494: 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

3255-697: Is still readily, although illegally, available in China and can be found in some illegally imported rat poisons. The best known Chinese rodenticide, containing about 6–20% TETS, is Dushuqiang, "very strong rat poison". It has been used for mass poisonings in China: in April 2004, there were 74 casualties after eating scallion-flavored pancakes tainted by their vendor's competitor; and in September 2002, 400 people were poisoned and 38 died from contaminated food. In 2002, there

3348-825: 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

3441-466: Is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. In an economic model , an exogenous change is one that comes from outside the model and is unexplained by the model. Such changes of an economic model from outside factors can include the influence of technology, in which this had previously been noted as an exogenous factor, but has rather been noted as

3534-405: 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

3627-536: 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

3720-575: 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

3813-521: 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

Tetramethylenedisulfotetramine - Misplaced Pages Continue

3906-539: 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

3999-436: 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

4092-439: 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

4185-637: 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

4278-448: 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

4371-477: 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

4464-449: 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

4557-432: 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

4650-462: The body. DNA introduced to cells via transfection or viral transduction is an exogenous factor. Exogenous factors in DNA, particularly DNA damage , are more known as environmental factors that cause progression in the impairment of DNA. Such exogenous factors would be different chemical agents, ionizing radiation (IR), and ultraviolet radiation (UV). These factors penetrate the deeper layers of

4743-448: The body. In philosophy , the origins of existence of self , or the identity of self, emanating from, or sustaining, outside the natural or influenced realm, are exogenous. Exogenous constructivism prioritizes the reconstruction of structures that have already been created in the environment, which is based from a mechanical metaphor, and greatly reflects off of Bandura 's social learning theory . Overall, exogenous constructivism

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4836-444: 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

4929-485: 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

5022-427: 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

5115-419: 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

5208-412: 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

5301-436: The brain stem. Curtis and Johnson were the first to hypothesize TETS antagonistic behavior on GABA. An in-vitro study using superior cervical ganglion neurons of rats found TETS to antagonize the depolarization actions of GABA, while having no influence on the cholinomimetic agent carbachol. This evidence suggests that TETS may act as a non-competitive inhibitor for GABA. Further research findings using crustacean models, indicated

5394-549: 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

5487-693: 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

5580-518: 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)

5673-427: The cell, causing great damage, with either apoptosis or senescence occurring, further leading to arrested or altered development and aging of the organism causing neurological disorders and cancer . In medicine , exogenous factors are seen in both pathogens and therapeutics . Exogenous factors can be included in the type of obesity where there is an imbalance of food and metabolism , in which one consumes

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5766-531: 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

5859-438: 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

5952-535: 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-

6045-498: 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

6138-401: 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

6231-455: 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

6324-449: 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

6417-463: 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

6510-399: 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

6603-636: 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

6696-411: 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

6789-408: 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

6882-425: 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

6975-415: The origins of diseases , exogenous factors, namely those that are factors of inflammation or stress , such as overexertion , overeating , and extreme feelings of emotions of grief or anger, all contribute to exhaustion or modifications in genes . An accumulation of such stressors affect the immune system by disrupting the amount of communication that occurs between the immune system and other areas of

7068-522: 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

7161-401: 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

7254-459: 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

7347-399: 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

7440-419: 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

7533-399: 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,

7626-425: The rodent populations. Rather than repel wandering scavengers, the chemical was proved to be toxic to the local rodent population for up to 4 years. Continued experiments conducted by the U.S. Forest Service found no direct effect between TETS and the gastro-intestinal or renal systems of spinal dogs. In this same study, no effects were seen within the peripheral or skeletal nerve system, limiting symptoms of toxicity to

7719-601: The same sample of mice, found that dual administration of diazepine and MK-801 had a synergistic protective effect against tonic-clonic seizures and 24-hour lethality, as opposed to clonic seizures that were poorly controlled. Sequential administration diazepine and MK-801 for clonic control of seizures in TETS exposed mice, may indicate the benefits of benzodiazepine-NMDA receptor antagonist regimens used to treat TETS exposed patients. Its use worldwide has been banned since 1984, but due to continuing demand and its ease of production, it

7812-539: 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

7905-401: 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

7998-432: 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

8091-499: 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

8184-549: 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

8277-422: 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

8370-407: 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

8463-404: 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

8556-512: The world. Exogeneity is proposed to ultimately cause geographic considerations to be rejected. In ludology , the study of games, an exogenous item is anything outside the game itself. Therefore, an item in a massively multiplayer online game would have exogenous value if people were buying it with real world money rather than in-game currency (though its in-game cost would be endogenous ). Noted as exogenous fantasy, one may also refer to this term as extrinsic stimuli or "fantasy"; these describe

8649-688: Was one documented case of accidental poisoning in the US. 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

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