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Neurotoxins
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Neurons are one of the main mechanisms of intracellular communication within the body. Bundles of neurons, known as nerves, are responsible for innervating muscles and organs, while neurons within the brain create the complex circuits and pathways responsible for a plethora of thought processes, biological responses, and vital functioning. The basic structure of a neuron is shown in Figure 1.
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Overview of Synaptic Transmission
Neurons rely on chemicals called neurotransmitters as their mode of communication, usually released from the axon terminals. Most neurons release only one type of NT at the axon terminal, but they are able to receive input from many different transmitters at the dendrites. The neurotransmitters move across the space between the neurons, called the synapse, and bind to receptor molecules on the membrane of the next neuron, referred to as the postsynaptic neuron. This binding can have a variety of effects on the postsynaptic cell, one of which is an action potential. An action potential travels down the axon towards the axon terminals via saltatory conduction. Here, vesicles of neurotransmitters are triggered to move to the membrane and release their contents into the next synapse. This sequence of events allows messages to travel through the body. Some neurons synapse directly to target organs or tissues, while others interconnect with other neurons. It should be noted that this process happens extremely quickly.
The neurons also have mechanisms of self-regulation and modulation, done by receptors on the pre-synaptic membrane*, called transporter molecules and auto-receptors. Transporter molecules 'reuptake', meaning they shuttle recently released neurotransmitters from the synapse back into the pre-synaptic cell for reuse. Auto-receptors act as a sensor for the pre-synaptic neuron by monitoring the amount of neurotransmitter released into the synapse. Feedback from these receptors typically decrease the amount of neurotransmitter released.
Any neuron can be referred to as a pre or post-synaptic neuron, depending on what aspect of the cell is being considered. For instance, if the neuron is receiving input from another cell, it is the post-synaptic, and when it signals to the next cell, it is the pre-synaptic cell.
The post-synaptic neuron contains yet another kind of receptors, mentioned above, called receptor molecules. There are two major subclasses, ionotropic and metabotropic, both of which are ligand-gated channels. A ligand is any substance that binds to a receptor molecule, which can be either endogenous (produced by the body) or exogenous (foreign to the body). Ionotropic receptors open immediately when an appropriate ligand binds. Metabotropic receptors, conversely, rely on a series of protein interactions in order to open. Exogenous ligands, upon binding, may act as either agonists, or antagonists. Agonists mimic an endogenous ligand and the receptor will respond as though the normal substance is attached. Antagonists, the opposite of an agonist, disrupt the normal receptor response to endogenous ligands.
Neurotoxin Mechanisms
Neurotoxins are chemical agents that affect the transmission of chemical signals between Neurons, causing a myriad of problems. Toxins can effect the cell at any step of neural transmission, or they may interact with neurotransmitters in the synapse. An overview of ways in which toxins interrupt neurons is outlined below.
| Presynaptic Disruptions | Presynaptic Effects |
|---|---|
| 1. Production of Neurotransmitters (NT's): Neurons produce transmitters with precursor molecules in the cell body. Many precursor molecules are acquired through diet. | 1. A lack of transmitter production prevents the release of transmitter from the presynaptic membrane. |
| 2. Axonal transport of transmitters: Some transmitters are transported down the length of a neuron by microtubules within in the cell. Certain drugs alter microtubule ability. | 2. Without properly functioning microtubules, transmitters will not be readily available for release into the synapse. |
| 3. Conduction of action potentials: Before the neuron sends a chemical signal into the synapse, it sends an electrical signal down the axon. Na+ channels are an essential part of this process, and some toxins block these channels. | 3. Preventing axonal conduction inhibits neuronal communication all together. The neuron can receive input, but it cannot send signals to other cells. |
| 4. Calcium-gated channels are essential for the release of transmitters from the axon terminal into the synapse. | 4. Prevents vesicles from moving to pre-synaptic membrane and signaling the next neuron. |
| 5. Transmitter storage within vesicles: Certain drugs allow transmitters to escape from the vesicle before the vesicle reaches the presynaptic membrane. | 5. When transmitters seep out of the vesicles, the vesicle still moves to the presynaptic membrane, but releases little if any transmitter into the synapse. |
| 6. Auto-receptors: auto-receptors, located on the presynaptic membrane, monitor and adjust the amount of transmitter being released into the synapse to avoid over stimulation of the adjacent cell. Usually these decrease the amount of transmitters being released. | 6. Alteration of an auto-receptor usually inhibits its regulatory action, causing the pre-synaptic neuron to release more transmitter. Occasionally, the auto-receptor will mistake a drug for a transmitter, and release fewer transmitters in response. |
| 7. Transporter molecules: These molecules, located on the presynaptic membrane, reuptake transmitters after they have bound to the postsynaptic cell and have been re-released. The transmitters are reusable by the cell, and can be repackaged and released again, however, not indefinitely. | 7. Blocking reuptake will cause an increased effect of that transmitter, because the transmitter will remain in the synapse longer and will continue to bind and rebind to the post-synaptic cell. |
| 8. Transmitter metabolism: Some transmitters are not reused by the presynaptic cell, but rather inactivated in the synapse by enzymes. MAO, or Monamine oxidase, is one such enzyme that can be disrupted by drugs or toxins. | 8. MAO inhibitors (MAOI's) disable the enzymes that usually inactivate certain transmitters, allowing them to have an increased effect on the adjacent cells. |
| Postsynaptic Disruptions | Postsynaptic Effects |
|---|---|
| 1. Changes in the number of postsynaptic receptors: Certain drugs can alter the amount of receptors present on the postsynaptic cell. Alcohol is an example of such a drug. | 1. Increasing or decreasing the amount of receptors on a neuron either increases or decreases the ease in which the drug can bind and take effect. |
| 2. Blocking receptor molecules: Preventing transmitters from binding to receptor molecules results in the failure of synaptic transmission. This can be done in two ways, the first of which is competitive binding where the drug binds in the same place a transmitter typically binds, called the active site. Noncompetitive binding similarly prevents transmission, however, in this case the drug does not bind to the active site, but rather a different part of the receptor, and causes the receptor to change shape or reject the transmitter. The general term for substances that thwart transmitter behavior is an antagonist. | 2. Blocking the entry of transmitters results in no effect in the post-synaptic neuron. |
| 3. Increasing receptor activity: Many types of drugs, bind to receptor molecules and act as transmitters. Drugs of this type are commonly referred to as agonists. | 3. Activating a receptor in the absence of the natural transmitter causes the post-synaptic neuron to respond as though the natural transmitter is present. However, since exogenous (foreign to the body) substances are not monitored by the pre-synaptic cell like transmitters, the post-synaptic cell response may be exaggerated. |
| 4. Altering second messengers: Certain drugs impede the 2nd messenger process essential for opening metabotropic receptors. | 4. Disrupting the action of 2nd messengers will obstruct the entry of the transmitters associated with that receptor. |
Neurotoxins
- Botulinum Toxin
- Polybrominated Diphenyl Ethers (PBDEs)
- Isobutyronitrile
- Hexachlorophene
- Metaldehyde
- Propoxur
- Hexane
- Styrene
Also see: Snakes
References
Breedlove, S. Marc, et al. Biological Psychology. Massachusetts: Sinauer Associates, Inc., 2007.
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