[Neurochemical aspect of brain aging--neuronal death and decreased synaptic functions]

Several diseases related to brain aging seem to be due to neuronal loss and decreased synaptic functions. Therefore it is important to clarify the cellular and molecular mechanism of age-related-neuronal death and -reduction in synaptic activities in the brain. I here review recent advances in cellular and molecular studies on neuronal death and the decrease in synaptic functions. Neuronal death is caused not only with physiological aging but also by several pathological states such as 1) results from abnormal metabolism of beta APP (Alzheimer's disease), 2) increased level of extraneuronal glutamate and intracellular Ca2+/NO (cerebral ischemia), and 3) appearance of neurotoxic MPP+ (1-methyl-4-phenyl-pyridinium ion) (Parkinson's disease) etc. From neurotoxicological aspect of neuro-glial interaction, I introduce recent findings on signaling pathways of NO synthase induction in glial cells and cytotoxic action of NO in neurons. Furthermore I also describe and discuss our findings obtained in the brain of old rats as well as in senescence accelerated mice (accelerated aging substrain of AKR/J-mouse) regarding age-related changes in synaptic activity and neurotransmittor receptor-mediated signaling system.