Glutamatergic neurotransmission in aging: a critical perspective

The effects of aging on glutamate neurotransmission in the brain is reviewe d and evaluated. Glutamate is the neurotransmitter in most of the excitator y synapses and appears to be involved in functions: such as motor behaviour , cognition and emotion, which alter with age. However, relatively few stud ies have been conducted to study the relationship between glutamate and agi ng of the brain. The studies presented here indicate the existence of a num ber of changes in the: glutamatergic system during the normal process of ag ing. First, an age-related decrease of glutamate content in tissue from cer ebral cortex and hippocampus has been reported, although it may be: mainly a consequence of changes in metabolic activity rather than glutamatergic ne urotransmission. On the other hand, studies in vitro and in vivo have shown no changes in glutamate release during aging. Since glutamate sampled in m ost of these studies is the result of a balance between release and uptake processes, the lack of changes in glutamate release may be due to compensat ory changes in glutamate uptake. In fact, a reduced glutamate uptake capaci ty, as well as a loss in the number of high affinity glutamate transporters in glutamatergic terminals of aged rats, have been described. However, the most significant and consistent finding is the decrease in the density of glutamatergic NMDA receptors with age. A new perspective, in which glutamat e interacts with other neurotransmitters to conform the substrates of speci fic circuits of the brain and its relevance to aging, is included in this r eview. In particular, studies from our laboratory suggest the existence of age-related changes in the interaction between glutamate and other neurotra nsmitters, e.g. dopamine and GABA, which are regionally specific. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.