IMMUNOHISTOCHEMICAL
STUDIES OF HERV-W AND NEUTRAL AMINO ACID TRANSPORTER (ASCT 1 AND 2) IN THE
BRAINS OF PATIENTS WITH SCHIZOPHRENIA, BIPOLAR DISORDER AND DEPRESSION
Serge Weis, Ida
C. Llenos. Stanley
Medical Research Institute and Departments of Psychiatry and Pathology,
Uniformed Services of the Health Sciences, Bethesda, MD
The present study was aimed
at the immunohistochemical demonstration of HERV-W proteins in the brain of
patients with schizophrenia, bipolar disorder and depression as well as of
normal controls. Antibodies against HERV-W SUTM, env and gag were provided by
Dr. Perron, Biomerieux, Lyon, France. In addition, potential receptors for
HERV-W were investigated, which included the neutral amino acid transporters 1
and 2. The cingulated gyrus (gray matter, white matter) and the hippocampal
formation (including 13 different subdivisions) were investigated in 15 brains
of each group.
HERV-W gag (3H1H6) was
expressed in neurons and glial cells in all control brains. Immunoreactivities
were seen on neurons, glial cells and neuropil. In the cingulated gyrus, there
was a significant decrease in staining intensity of neurons in schizophrenia and
bipolar disorder compared to controls, while no changes were seen in the density
of stained neurons. No significant changes were seen for glial cells in the
gray and white matter. In the hippocampal formation, the staining intensity and
density of glial cells was significantly reduced in the brains of patients with
schizophrenia and bipolar disorder in most of the 13 subdivisions. The
reduction in glial immunoreactivities was significant in 8 of the 13
subdivisions in the schizophrenic group and 7 of 13 subdivisions in patients
with bipolar disorder. The immunoreactivities over axons were significantly
reduced in schizophrenia, while these changes were also apparent in many
hippocampal subdivisions of bipolar brains. Significant reduction in
immunoreactivities were found for neurons and interneurons in schizophrenia and
bipolar disorder.
The neutral amino acid
transporters 1 and 2 showed significant reductions in reactivities in glial
cells of the white matter in the cingulated gyrus in patients with schizophrenia
whereas the gray matter glial cells were not affected. These differences were
not seen in the brains of patients with bipolar disorder. No significant
changes were noted in the brains of patients with major depression. The
immunoreactivities for ASCT 1 and 2 on neurons were significantly reduced in
schizophrenia and bipolar disorder, but not in major depression.
In conclusion, the
expression of HERV-W gag at the protein level is significantly reduced in
schizophrenia and bipolar disorder compared to controls, whereas the brains of
depressed patients do not show any significant differences compared to
controls. The expression of neutral amino acid transporters is likewise reduced
in schizophrenia and bipolar disorder. Future studies should clarify the
mechanisms leading to the reduced expression of HERV-W gag and elucidate its
functional sequelae. Furthermore, the significance of the expression of HERV-W
gag in normal controls has to be established.