What Is a Neurotoxicity?

Neurotoxins are toxic substances that are destructive to nerve tissue. Such as AF64A, 6-hydroxydopamine and kainic acid. AF64A can selectively destroy cholinergic neurons. 6-Hydroxydopamine can selectively destroy dopamine, norepinephrine and epinephrine neurons, and is easily taken up by catecholamine neurons. Generally injected into the brain for about 5-7 days can degenerate neurons, but cannot destroy 5 Serotonin neurons. Kaimaric acid is highly selective in the destruction of neural tissue and can damage the cell body of neurons without damaging nerve fibers. Due to its selective destructive effect on neural tissue, it is often used to prepare animal models of advanced psychological dysfunction. ^[1]

Can often cause neurotoxins (such as snake venom) and presynaptic neurotoxins. Also acts on axons (such as

Neurotoxin was developed from civil organophosphorus pesticides. In 1935, German scholars successfully developed fast-acting organophosphorus pesticides.

Neurotoxic agent ^[2]

Most insecticides have strong neurotoxicity, and they have different targets on the nervous system. Organophosphorus pesticides not only inhibit acetylcholinesterase activity and acetylcholine receptor function. Affects the release of acetylcholine, but also has non-cholinergic toxicity. Some organophosphate insecticides can also cause delayed neurotoxicity. Neonicotinoid insecticides, as agonists of the nicotinic acetylcholine receptor (nAchR), act on the a subunit of this type of receptor; it is much more toxic to insects than mammals, because It has different sites of action on insect and mammalian nAchR. Pyrethroid insecticides mainly act on sodium channels of nerve cells, causing continuous opening, leading to conduction block; this class of insecticides can also inhibit calcium channels. In addition, such pesticides interfere with the release of glutamate and dopamine neurotransmitters. The selective toxicity of pyrethroid insecticides to insects is probably due to the difference in the structure of sodium channels of insect neurons and mammals. Avermectin-type insecticides mainly act on GABA receptors, which can promote the release of cABA, enhance the binding of cABA and cABA receptors, increase the influx of chloride ions, and cause supersynaptic membrane Into. Because it is difficult for these insecticides to penetrate the blood-brain barrier of vertebrates and bind to the GABA receptors of the central nervous system, their toxicity to vertebrates is much lower than that of insects. Spinosad insecticides can interact with nAchR in the central nervous system, causing long-term release of Ach. In addition, these insecticides can also act on cABA receptors in insects and change the function of GABA-gated chloride channels ^[3]

Manganese is a silver-gray black metal with lively chemical properties. It is an essential trace element in the body and plays an important role in the body. But long-term exposure to high-concentration manganese soot will cause chronic manganese poisoning. Its clinical manifestations, pathology, and neurobiochemistry closely resemble neurodegenerative disease-Parkinson's disease, with symptoms of damage to the extrapyramidal system of the central nervous system and tremor paralysis. The lesions are located in the striatum, lenticular nuclei, and tail of the basal ganglia. Nuclei, paleospheres, thalamus and brainstem ganglia. Cells can be seen under the microscope with gel-like degeneration and degeneration, especially in the basal ganglia. In addition, there are changes in the neurotransmitter dopamine and its metabolites. More and more research data indicate that there is a positive correlation between environmental risk factors such as exposure to heavy metals and other inorganic toxicants such as pesticides and idiopathic elderly PD. Manganese has been considered as one of the main environmental factors of PD ^[4]

Acrylamide poisoning is characterized by weak limbs and ataxia. Animals generally experience agitation, irritability, burnout, reduced active activity, reduced orthostatic reflexes, reduced sensory movement, shorter runner balance time, unstable gait swing, increased hind limb support test extension, and weakness or paralysis of hind limbs. Behavioral changes are related to dose, duration, and mode of exposure.

Acrylamide binds and inhibits kinesin, which directly reduces the number of vesicles moving in the rapid forward transport system. Although kinesin can be compensated by resynthesis, repeated inhibition of kinesin results in rapid axonal distal or peripheral axons Progressive lack of transporters, functional inhibition; meanwhile, the direct axonal inhibition of cytoplasmic dynein or the slowing of rapid forward transport indirectly inhibits reverse axonal transport, changes in nutritional signals or axonal vesicles The overload of other enzymes suggests that ACR also acts on other axon proteins, such as enzymes and dyneins involved in axon transport. When the above interference or damage exceeds the body's ability to maintain or compensate, axonal or peripheral pathological changes or behavioral dysfunctions occur, leading to neuropathy