Term Paper Proposal axl90

Neurotoxin

Neurotoxin (from Ancient Greek: νευρών neuron “sinew” and τοξικόν toxikon “toxin”) is classification given to an extensive category of neurological insults (Spencer 2000) which can adversely affect both developing and mature nervous tissue (Olney 2002), and includes chemicals, biological compounds, and physical agents such as extremes of heat and cold. Common examples of neurotoxins include lead (Lidsky 2003), ethanol (Heaton 2000), phencyclidine (PCP), ketamine, glutamate (Choi 1987), nitric oxide (NO) (Dawson 1991), β-Amyloid peptide (βAP) (Hensely 1994), and tetrodotoxin (Kiernan 2005). Often neurotoxin activity is characterized by interruptions to ion channels such as the glutamate receptors, NMDA and GABA (Choi 1988), or Na channels (Kiernan 2005). Local pathology of neurotoxin exposure often includes neuron excitotoxicity or apoptosis (Dikranian 2001), but can also include glial cell damage (Deng 2003). Macroscopic manifestations of neurotoxin exposure can include widespread central nervous system damage such as retardation (Olney 2002), persistent memory impairments (Jevtovic-Todorovic 2003), Huntington's disease (Coyle 1976), epilepsy, and dementia (Nadler 1978). Additionally, neurotoxin-mediated peripheral nervous system damage such as neuropathy or myopathy is common. Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant (Heaton 2000) and ethanol (Takadera 1990) administration.

Notes (Not to be included in final article)

Ions can play a role in regulating neurotoxicity of compounds, as seen during chemically induced hypoxia where intracellular Ca accumulation leads to neuron necrosis, but inhibition of Ca accumulation protects from injury (Choi 1988).

Neurotoxins are often most biologically influential during synaptogenesis, as this period is characterized by rapid nervous system growth and development as well as a hypersensitivity neurons to external disturbances (Olney 2002).

Disturbances from compounds of this nature induce neuron degeneration through altered glutamate and GABA neurotransmitter release patterns including altered NMDA and GAMA receptor activity, resulting in excitotoxicity or apoptosis, two mechanisms by which neurotoxins may manifest their effects.

Excitotoxicity is necrosis in response to hyperstimulation, and apoptosis is a physiologically programmed suicidal process by which redundant or unsuccessful neurons are eliminated (Dikranian 2001).

NMDA antagonists and GABAmimetics are a category of compounds used to induce general anesthesia, and have been shown to induced general apoptotic neurodegeneration during synaptogenesis, resulting in persistent memory and learning impairments (Jevtovic-Todorovic 2003).

Neurotoxins can also function through disruption of glial cell function such that insults to astrocytes, oligodendrocytes, and Schwann cells will involve subsequent induced neuron apoptosis (Deng 2003).

It is also possible that compounds essential to neuron function can act as neurotoxins, as glutamate, an important NT can function both in excitatory signaling, and as a toxin when in high concentrations (Choi 1987). Effects of widespread glutamate neurotoxicity can lead to complications such as Hunington’s disease (Coyle 1976), epilepsy, and dementia (Nadler 1978).

The number of known neurotoxins is extensive, with recent evidence being shown for 372 known substances possessing evident neurotoxicity (Spencer 2000).

NO can act as neurotoxin (Dawson 1991).

Neuronal injury can be ameliorated by the intake of antioxidants (Lafon-Cazal 1993), an example being ethanol leads to loss of Purkinje cells in the Cerebellum in fetuses, which can be rescued by the intake of substantial quantities of vitamin E (Heaton 2000).

β-Amyloid peptide (βAP) which is an important factor of Alzheimer’s disease can potentiate glutamate excitotoxicity (Hensley 1994).

Often neurotoxins function through the inhibition of ion channels, such as tetrodotoxin from the puffer fish which inhibits functionality of Na channels leading to (Kiernan 2005).

Ethanol can inhibit NMDA mediated Ca influx leading to reduced excitotoxicity (Takadera 1990).

Ca accumulation occurs in response to a number of insults, including epilepsy, physical trauma, and ischemia, suggesting its importance in providing a controlling mechanism for acute neuronal degeneration and delayed neurotoxicity (Tymianski 1993).

References

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--Liggett 15:01, 19 October 2011 (UTC)