Neurotoxins are toxins that are poisonous or 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 is important in the study of
nervous systems. Common examples of neurotoxins include lead,
ethanol (drinking alcohol), manganese 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 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 is common. Support has
been shown for a number of treatments aimed at attenuating
neurotoxin-mediated injury, such as antioxidant and antitoxin
2 Applications in neuroscience
3 Mechanisms of activity
3.1.1 Sodium channel
3.1.2 Potassium channel
3.1.3 Chloride channel
3.1.4 Calcium channel
3.1.5 Synaptic vesicle release
220.127.116.11 Botulinum toxin
Blood brain barrier
3.2 Receptor agonists and antagonists
3.4 Calcium-mediated cytotoxicity
3.5 Neurotoxins with multiple effects
3.7 Receptor-selective neurotoxins
Endogenous neurotoxin sources
3.8.1 Nitric oxide
4 See also
7 Further reading
8 External links
Illustration of typical multipolar neuron
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
Roman Empire resulting from 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 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 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 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 a number of potential chemical insults.
Astrocytes surrounding capillaries in the brain to form the blood
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 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 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 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
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 the more common in vivo systems
of the past. Examples of improvements include tractable, uniform
environments, and the elimination of contaminating effects of systemic
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 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 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 the inhibition of acetylcholinesterase
capacity of organophosphates (includes DDT 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.
Applications in neuroscience
Though diverse in chemical properties and functions, neurotoxins share
the common property that they act by some mechanism leading to either
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 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
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 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
Mechanisms of activity
As neurotoxins are compounds which adversely affect 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 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.
Na channel inhibitors
K channel inhibitors
Cl channel inhibitors
Ca channel inhibitors
Inhibitors of synaptic vesicle release
Botulinum toxin, tetanus toxin
Blood brain barrier inhibitors
Endogenous neurotoxin sources
Nitric oxide, Glutamate, Dopamine
The puffer fish is a well known tetrodotoxin producer.
Tetrodotoxin (TTX) is a poison produced by organisms belonging to the
Tetradontidae order, which includes the puffer fish, ocean sunfish,
and porcupine fish. Within the puffer fish, which is a common
delicacy especially in Japan, TTX is found in the liver, gonads,
ovaries, 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
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 the sodium current that drives the
depolarization phase of neuron action potentials.
Inhibited signaling response resulting from neuron exposure to
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 significant
levels 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 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
Neostigmine or 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 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 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 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
Chlorotoxin (Cltx) is the active compound found in scorpion venom, and
is primarily toxic because of its ability to inhibit 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 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 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 the
membranes of neurons but not those of muscle cells.
Synaptic vesicle release
Mechanism of 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 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 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 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 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.
Blood brain barrier
Neurotoxic behavior of aluminum is known to occur upon entry into the
circulatory system, where it can migrate to 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 the blood, such as
those experiencing renal failure. Patients experiencing aluminum
toxicity can exhibit symptoms such as impaired learning and reduced
motor coordination. Additionally, systemic aluminum 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, aluminum is
still extensively utilized in the packaging and preparing of food,
while other toxic metals such as lead have been almost entirely
phased-out of use in these industries.
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 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.
Receptor agonists and antagonists
University of Nottingham
Investigations into anatoxin-a, also known as "Very Fast Death
Factor", began in 1961 following 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-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 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, 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 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 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 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 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 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 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 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
Arsenic 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 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 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
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
An Astrocyte, a cell notable for maintaining the blood brain barrier
Ammonia toxicity 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 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, the toxic effects of ammonia on astrocyte remodling 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.
Lead pipes are common sources of ingested lead.
Lead 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 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 a result of
early lead exposure. In addition to inducing apoptosis, lead
inhibits interneuron signaling through the disruption of
calcium-mediated neurotransmitter release.
Neurotoxins with multiple effects
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 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 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
NMDA receptor activity, and thus reduces 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 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 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.
Hexane is a neurotoxin which has been responsible for the poisoning
of several workers in Chinese electronics factories in recent
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 the presentation of permanent
parkinsonism in exposed subjects 2–3 days after administration.
Endogenous neurotoxin sources
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 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 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 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 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.
Dopamine is an endogenous compound that is used as a neurotransmitter
to modulate reward expectation.
Dopamine kills dopamine-producing
neurons by interfering with the electron transport chain in neurons.
This interference results in an inhibition of cellular respiration,
leading to neuron death.
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Wikimedia Commons has media related to Neurotoxins.
Environmental Protection Agency at United States Environmental
Alcohol and Alcoholism at Oxford Medical Journals
Neurotoxicology at Elsevier Journals
Neurotoxin Institute at
Neurotoxins at Toxipedia
Spooky toxin (SsTx)
Outline of neuroscience
Molecular cellular cognition
Neural network (artificial)
Neural network (biological)
Intraoperative neurophysiological monitoring
Staphylococcus aureus alpha/beta/delta
Toxic shock syndrome toxin
Enterotoxin B (SEB)
Verotoxin/shiga-like toxin (E. coli)
E. coli heat-stable enterotoxin/enterotoxin
Extracellular adenylate cyclase
Bacillus thuringiensis delta endotoxin
Clumping factor A
Fibronectin binding protein A
Amatoxin (alpha-amanitin, beta-amanitin, gamma-amanitin,
Androctonus australis hector insect toxin
note: some toxins are produced by lower species and pass through