Expression of cellular prion protein (PrPc) in schizophrenia, bipolar disorder, and depression

Cellular prion protein (PrPc) is a copper-binding, membrane-attached GPI-anchored glycoprotein characterized by a high degree of amino acid sequence conservation among mammals. PrPc expression has been demonstrated in neurons, microglia, lymphocytes, and keratinocytes. Recently, the concept that PrPc may be involved in the defense against oxidative stress was advanced. In the present study, we used immunohistochemistry for PrPc to investigate 60 brains from the Stanley Neuropathology Consortium (15 controls, 15 patients with schizophrenia, 15 with bipolar disorder, and 15 with major depression). Rating scores as well as the numerical density of PrPc-positive and -negative neurons and glial cells were determined in the cingulate gyrus. All four groups showed a very high interindividual variation. PrPc-positive glial cells were significantly reduced in the white matter of patients with schizophrenia, bipolar disorder, and major depression. A similar result was obtained for the white matter in bipolar patients using rating scales. From the confounding variables, use of medication (i.e. antipsychotics, antidepressants, and mood stabilizers) had a significant effect on the expression of PrPc by neurons and glial cells. PrPc-immunoreactivities were significantly reduced for white matter glial cells in all examined groups. However, the results are not indicative for the occurrence of oxidative stress in the brains of schizophrenic and bipolar patients. Since the effect of antipsychotic and antidepressant medication as well as of mood stabilizers on the expression of PrPc was significant, it needs further clarification in experimental models.