NMDA brain development

Thus, a GSH deficit has consequences consistent with the concept of functional disconnectivity, as hypofunction of NMDA-R and alteration of dopamine signaling have been observed. When imposed on animals during development, a GSH deficit induces also a structural disconnectivity, as revealed by the decrease in dendritic spines and parvalbumin-immunoreactivity of inhibitory intemeurons in the prefrontal cortex Finally, a transient GSH deficit during brain development causes deficits in visual recognition and olfactory integration. 

We propose that a redox/antioxidant dysregulation due to GSH deficit could represent a vulnerability factor at the early phase of brain development in at least a subgroup of schizophrenia patients. Combined with other genetic factors and environmental factors, such as stress, obstetrical complications or viral infections, it could favor the development of the disease. The role of the GSH deficit proposed allows integration in a causal way many phenomenological aspects of schizophrenia. It is compatible with both the DA and the glutamate/NMDA hypotheses and with the neuropathological observations. In contrast to... 

Vaccarino, A. L., Marek, P., Kest, B., Weber, E., Keana, J. F. W., Liebeskind, J. C. NMDA receptor antagonists, MK-801 and ACEA-1011, prevent the development of tonic pain following subcutaneous formalin, Brain Res. 1993, 615, 331-334. 

The stargazer mutant mouse is ataxic and epileptic. It lacks functional AMPA receptors (Fig. 30-1), which apparently are not delivered successfully to the synapses in the cerebellum in which they function.380 386 Mutation of a transmembrane protein stargazin, which may interact with the AMP receptor, causes the symptoms.457 458 NMDA receptors (Fig. 30-20) are involved in synapse formation in the brain. Filopodial extensions on dendrites, triggered by electrical activity, are essential for synapse formation,459 which occurs rapidly.4593 Activation of NMDA receptors is apparently also necessary.379 460 Without this stimulation the excitatory glutamatergic neurons of the developing brain undergo apoptosis. 

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