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ORGANISATION FOR THE PROHIBITION OF CHEMICAL WEAPONS Working Together for a World Free of Chemical Weapons Neurochemistry of Toxins Edoxie E. Allier-Gagneur, Wesam S. Alwan and Jonathan E. Forman The Central Nervous System (CNS) is composed of the brain and spinal cord; it coordinates thoughts, memory and other complex processes, such as the body’s reaction to stimuli. A synapse is the gap between two nerve cells (neurons) through which chemical signalling molecules (neurotransmitters) pass to ensure communication between nerve endings. There are several types of neurotransmitters; excitatory such as glutamate (in the brain) and acetylcholine (in the muscle and in the brain) or inhibitory, such as gamma-aminobutyric acid (GABA; present in the brain). There are three types of neurons: motor-, sensory- and inter-neurons. Sensory neurons are present in eyes, nose, skin and ears; they relay information about the environment to the CNS. Motor neurons send information to the muscles and glands; controlling movement and reaction. Interneurons are cells that connect other neurons. Parietal lobe @opcw @opcw_st Occipital lobe /opcwonline Frontal lobe Ammonia Temporal lobe /opcwonline /company/opcw /opcw Induces swelling of astrocytes (cells that protect neurons) which slows brain function. Cerebellum Spinal cord LD50= 3.5 x 107 ng/kg Ethanol Reduces the stability of membranes, which can prevent neurotransmitters release and binding, disabling communication between neurons. Tetanus Toxin LD50= 8.3 x 109 ng/kg Disables inhibitory neurons (those sending an “off” signal) resulting in excessive muscle contraction. Presynaptic neuron Caramboxin LD50= 2 ng/kg Synapse Glutamate Is an endogenous neurotransmitter, responsible for the transmission of an excitatory signal to the postsynaptic neuron. Postsynaptic neuron Arsenic in the form of soluble As3+ Glutamate Receptor Calcium (Ca2+) Channel Glutamate (Neurotransmitter) When present in excess, glutamate induces a calcium flux into the neuron; this can lead to swelling and necrosis. LD50= 1.7 x 104 ng/kg Overstimulates glutamate receptors, effectively producing a state similar to that of an excessive level of glutamate. GABA (Inhibitory Neurotransmitter) Astrocyte (Protective cell) Point of initiation of toxin effect Cellular membrane Long term inhibition of neuron growth; short term increase of intra-cellular Ca2+ levels; this in turn can induce cell death. LD50= 2 x 107 ng/kg