REDUCED EXPRESSION OF HUMAN ENDOGENOUS RETROVIRUS (HERV)-W GAG PROTEIN IN THE CINGULATE GYRUS AND HIPPOCAMPUS IN SCHIZOPHRENIA, BIPOLAR DISORDER, AND DEPRESSON
J Neural Transm. 2007 May; 114(5):645-55. Epub 2007 Jan 15
Weiss S, Llenos IC, Sabunciyan S, Dulay JR, Isler L, Yolken R, Perron H.
Laboratory of Brain Research and Neuropathology, Departments of Psychiatry and Pathology, Uniformed Services, University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD U.S.A.
The Human endogenous retrovirus (HERV)-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis associated retroviral element (MSRV). Upregulation of the HERV-W POL has been reported in cerebrospinal fluid of patients with schizophrenia. The expression of capsid (GAG) protein of HERV-W was studied by immunohistochemistry and western blotting in postmortem brain tissue of the anterior cingulated cortex and hippocampal formation of normal controls and of patients with schizophrenia, bipolar disorder and major depression. A physiological expression of GAG protein was detected in neurons as well as astroglial cells in normal brain both in the anterior cingulated cortex and in the hippocampal formation. There was a statistically significant reduction of this expression in neurons and astroglial cells in brains from individuals with schizophrenia, major depression, and bipolar disorder. The results from the present study confirm that GAG protein encoded by the HERV-W multicopy gene family isexpressed in cells of the central nervous system under normal conditions. Our findings of a cell type -, brain region- and disease-specific reduced expression in schizophrenia, major depression, and bipolar disorder are compatible with a pathophysiological role of HERVs in human brain disorders. The causes and biological consequencds of this differential regulation will be the subject of further investigations.