Neurotransmitters

Dopamine is the primary neurotransmitter in the basal ganglia (i.e., striatum, substantia nigra) and to a lesser extent in the cerebral cortex. In normal aging there are presynaptic alterations including decline of dopamine in the striatum, decreased dopamine metabolites (indicated by decreased dopamine biosynthesis), as well as postsynaptic alterations including decreased dopamine receptors. As summarized in the review by Morgan and Finch, the decline in the DA content and TH activity of the substantia nigra and striatum of aged rodents is not a consistent finding across rodent species and is generally smaller than that reported for nonhuman primate and postmortem human brains. Similarly, for dopamine cell loss, while it has been reported that normal aging is not associated with a significant decline in the total number of DA neurons of the substantia nigra in aged mice, controversy exists as to the degree DA cell loss occurs in the substantia nigra of nonhuman primates and man. It is interesting that despite the fact that there are presently five different classes of dopamine receptors, the decline in the D2 receptor is the only one that has been reported to show an age-related decline across species. The reasons for this variability are yet unclear. Other age changes seen in the dopaminergic system included decreased dopamine transporter (responsible for uptake of dopamine from the synapse) and increased monoamine oxidase B (an enzyme that breaks down dopamine resulting in reduced effective synaptic levels of dopamine). The prime example of a neurogenerative disease associated with the loss of dopamine neurons is Parkinson's disease.