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Abstract:
Alterations of postsynaptic density (PSD)95-complex proteins in
schizophrenia ostensibly induce deficits in synaptic plasticity, the
molecular process underlying cognitive functions. Although some
PSD95-complex proteins have been previously examined in the hippocampus
in schizophrenia, the status of other equally important molecules is
unclear. This is especially true in the cornu ammonis (CA)1 hippocampal
subfield, a region that is critically involved in the pathophysiology of
the illness. We thus performed a quantitative immunoblot experiment to
examine PSD95 and several of its associated proteins in the CA1 region,
using post mortem brain samples derived from schizophrenia subjects with
age-, sex-, and post mortem interval-matched controls (n=20/group). Our
results indicate a substantial reduction in PSD95 protein expression
(-61.8%). Further analysis showed additional alterations to the scaffold
protein Homer1 (Homer1a: +42.9%, Homer1b/c: -24.6%), with a twofold
reduction in the ratio of Homer1b/c:Homer1a isoforms (P=0.011).
Metabotropic glutamate receptor 1 (mGluR1) protein levels were
significantly reduced (-32.7%), and Preso, a protein that supports
interactions between Homer1 or PSD95 with mGluR1, was elevated (+83.3%).
Significant reduction in synaptophysin (-27.8%) was also detected, which
is a validated marker of synaptic density. These findings support the
presence of extensive molecular abnormalities to PSD95 and several of
its associated proteins in the CA1 region in schizophrenia, offering a
small but significant step toward understanding how proteins in the PSD
are altered in the schizophrenia brain, and their relevance to overall
hippocampal and cognitive dysfunction in the illness.
