Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment.
The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.
Konradi
Christine
C
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA. konradi@mclean.harvard.edu
Heckers
Stephan
S
D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005971:Glutamates / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology; D017470:Receptors, Glutamate / Q000145:classification / Q000502:physiology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D014150:Antipsychotic Agents; D005971:Glutamates; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate