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Published on: October 5, 2012
Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia
L F Jarskog1, J H Gilmore, E S Selinger
1Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Background:
The etiology of schizophrenia remains unknown; however, a role for apoptosis has been hypothesized. Bcl-2 is a potent inhibitor of apoptosis and also exerts neurotrophic activity in the central nervous system (CNS). Bcl-2 expression is increased in the CNS of several neurodegenerative disorders. Given that schizophrenia has certain features of a limited neurodegenerative disorder, it was hypothesized that cortical Bcl-2 expression is increased in schizophrenia.
Methods:
Postmortem temporal cortex was obtained from the Stanley Foundation Neuropathology Consortium with matched control, schizophrenic, bipolar, and depressed subjects. Bcl-2 protein was measured by enzyme-linked immunoassay (ELISA) and Western blot. Primary analysis was limited to schizophrenia versus control subjects.
Results:
The ELISA demonstrated 25% less Bcl-2 protein in schizophrenia (p =.046), supported by Western blot results. A secondary analysis of schizophrenic and bipolar subjects revealed twofold higher mean Bcl-2 in antipsychotic-treated versus neuroleptic-naive subjects.
Conclusions:
Contrary to our hypothesis, cortical Bcl-2 was reduced in schizophrenia. This supports the notion that schizophrenia is not a classic neurodegenerative disorder; however, less Bcl-2 protein may signal neuronal vulnerability to proapoptotic stimuli and to neuronal atrophy. Also, the association between neuroleptic exposure and higher Bcl-2 levels could underlie the favorable long-term outcomes of patients who receive maintenance antipsychotic treatment.
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