Increased extracellular clusterin in the prefrontal cortex in schizophrenia

Abstract

The expression of the gene that encodes clusterin, a glycoprotein that has been implicated in the regulation of many cellular processes, has previously been found in gene expression profiling studies to be among the most significantly differentially expressed genes in pyramidal and parvalbumin-containing inhibitory neurons in the cerebral cortex in subjects with schizophrenia. In this study, we investigated whether clusterin may also be dysregulated at the protein level in schizophrenia subjects. We found that, although the intracellular amount of clusterin may be unchanged, the level of extracellular, secreted clusterin appears to be significantly increased in schizophrenia subjects. It is speculated that this finding may represent a neuroprotective response to pathophysiological events that underlie schizophrenia.

Keywords: Clusterin; Schizophrenia.

Figure 1

A. Photomicrograph showing the distribution of clusterin-immunoreactive cells in the human prefrontal cortex in a control subject. Scale bar=50 μm. B. Cell plots showing that the densities of cluster-immunoreactive cells are unaltered in a schizophrenia (right) compared a normal control (left) subjects. Blue circles= non-pyramidal cells, yellow circles= glia, and green circules=pyramidal cells.

Figure 2

Densities of clusterin-immunoreactive pyramidal cells (PYR), nonpyramidal interneurons (IN) and glias (GL) in the prefrontal cortex are unchanged in schizophrenia subjects.

Figure 3

A. The amount of extracellular clusterin as measured by fluorescent intensity is significantly (p=0.014) increased in schizophrenia subjects (mean±SD=1.25±0.08) compared to normal control subjects (mean±SD=0.97±0.07). B. Western blot showing averaged fluorescent intensities of extracellular and intracellular forms of cluster in schizophrenia (SZ) and control (C) subjects. Band 1=extracellular form of clusterin, band 2 and band 3=intracellular forms of clusterin.