Calcium dependent aspects of synaptic plasticity, excitatory amino acid neurotransmission, brain aging and schizophrenia: a unifying hypothesis.

(1) The functional and structural reorganization of dendritic spines by calcium activated proteases is postulated to play a causal role in the production of the phenomenology of brain aging and in particular in the development of pathology and degeneration. Excitatory neurotransmission appears to be essential for the development of irreversible synaptic changes. (2) One of the genes modified in schizophrenia is postulated to be directly or indirectly linked to the control of excitatory neurotransmission; possibly the normal switching on of the expression of the adult form of the NMDA receptor is altered, resulting in an inappropriate functioning of this receptor. This genetic characteristic might explain the apparent resistance of schizophrenic brains to aging.