Allostasis, allostatic load, and the aging nervous system: Role of excitatory amino acids and excitotoxicity

The adaptive responses of the body to challenges, often known as "stressors ", consists of active responses that maintain homeostasis. This process of adaptation is known as "allostasis", meaning "achieving stability through c hange". Many systems of the body show allostasis, including the autonomic n ervous system and hypothalamo-pituitary-adrenal (HPA) axis and they help to re-establish or maintain homeostasis through adaptation. The brain also sh ows allostasis, involving the activation of nerve cell activity and the rel ease of neurotransmitters. When the individual is challenged repeatedly or when the allostatic systems remain turned on when no longer needed, the med iators of allostasis can produce a wear and tear on the body that has been termed "allostatic load". Examples of allostatic load include the accumulat ion of abdominal fat, the loss of bone minerals and the atrophy of nerve ce lls in the hippocampus. Circulating stress hormones play a key role, and, i n the hippocampus, excitatory amino acids and NMDA receptors are important mediators of neuronal atrophy. The aging brain seems to be more vulnerable to such effects, although there are considerable individual differences in vulnerability that can be developmentally determined. Yet, at the same time , excitatory amino acids and NMDA receptors mediate important types of plas ticity in the hippocampus. Moreover, the brain retains considerable resilie nce in the face of stress, and estrogens appear to play a role in this resi lience. This review discusses the current status of work on underlying mech anisms for these effects.