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精神分裂症海马突触蛋白表明CA3神经活动增加

   Synaptic Proteins In Schizophrenia Hippocampus Indicate Increased Neuronal Activity in CA3

    Am J Psychiatry. Author manuscript; available in PMC 2015 Jun 5.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457341/

  Abstract

  In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on a model of hippocampal dysfunction in schizophrenic psychosis, we postulated increased NMDA receptor signaling in CA3. Here we demonstrate that the GluN2B-containing NMDA receptors (GluN2B/GluN1) and its associated postsynaptic membrane protein PSD95 are both increased in human hippocampal CA3 from schizophrenia cases, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons show an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. AMPA receptor subunit proteins are not altered in CA3 or CA1 subfields, nor are several additional related signaling proteins. These hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state which may contribute to development of long term potentiation with subsequent stimulation and ‘un-silencing’. These changes are plausibly associated with increased associational activity in CA3, degraded declarative memory function and with psychotic manifestations in schizophrenia. The influence of these hyperactive hippocampal projections onto targets in limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.

  Keywords: Hippocampal subfields, Psychosis, Golgi staining, spines, dendritic length, GluN2B subunits, PSD95 protein, activity-dependent signaling