IMMUNOHISTOCHEMICAL STUDIES OF HERV

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.