Neurotransmitters

GABA and glutamate are both metabolic intermediates and neurotransmitters. GABA is considered the major inhibitory neurotransmitter in the brain, whereas glutamate is considered an excitatory neurotransmitter that promotes a postsynaptic stimulatory response. In the aged brain glutamic acid decarboxylase (GAD), the enzyme that converts glutamate into GABA, falls 20–30 percent in the cortex and thalamus of postmortem human brain, and there is a decrease in GABA receptor binding sites and GAD mRNA levels in the aged rodent brain. Similarly, previous studies have reported an age-related decrease in glutamate receptors in the hippocampus of aged rats, mice, and nonhuman primates while no change in glutamate receptor binding sites has been found in postmortem human brains. Huntington's disease is the classic example of a neurodegenerative disease linked to the loss of GABA neurons in the striatum.

To summarize, while there is little doubt that degenerative changes occur in neurons of the aged brain the severity of these changes vary from person to person, and the question of cause and effect remains elusive. In addition, previous studies have shown that age-related changes in the neurotransmitter systems of the brain are not a global phenomenon of normal aging but are brain region, cell type, and species specific. Species variability is well documented in the gerontologic literature, and we must be cautious in our interpretations when comparing data across animal species or when comparing cellular changes in animals and human aging. Lastly, it is no longer possible to associate brain aging with the loss of function and structure without taking into consideration the compensatory or plastic nature of the nervous system. Rather, it is understood that the aging brain represents a composite of various adaptive and compensatory responses, which work together to maintain neurotransmitter levels in the brain and repair the brain's neural networks in response to naturally occurring cell loss or neurochemical changes that are brain region specific.