Neurotransmitters

The neurotransmitter acetylcholine is important for communication in a number of brain regions, particularly the hippocampus, striatum, and cerebral cortex. It is also the neurotransmitter used to transmit information at the neuromuscular junction. Acetylcholine is synthesized presynaptically by the enzyme choline acetyltransferase (CAT). Absolute levels of CAT and its activity decline with age, ranging from a 20 to 30 percent decline in the hippocampus and striatum and about a 10 percent decline in the cerebral cortex. Within these same anatomical regions there is evidence of some neuron cell loss, but it does not necessarily account for total decline in neurotransmitter production. It is interesting that the loss of CAT activity can be reversed or attenuated. For example, increased production of neurotrophic factors (which themselves are regulated by exercise and diet) influence CAT activity and acetylcholine production. In addition to these presynaptic changes, postsynaptic alterations have also been documented. For example, the muscarinic acetylcholine receptor, the synaptic receptor protein that binds acetylcholine, has been shown to decline by similar degrees in areas where CAT activity is also diminished. However, it remains to be determined whether this is the cause of the neurotransmitter deficiency or a consequence in response to presynaptic changes. Despite the fact that global neuron cell death may not underlie specificity of neurotransmitter system decline, some studies, but not all, have suggested that altered cholinergic neurotransmission may also be accompanied by a decline in the number or size (atrophy) of cholinergic neurons, including those in the nucleus basalis. The best example of a neurodegenerative disease associated with the loss of cholinergic neurons is Alzheimer's disease.