Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Nakhlas, M.
Apoptosis in Schizophrenia, Bipolar Disorder and Major Depression
Studium für die Gleichwertigkeit; Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2015. pp. 64
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Beham-Schmid Christine
- Haybäck Johannes
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- Abstract:
- Background Apoptosis is an essential component of neuronal development, and dysregulation of apoptosis in the limbic system has been recently implicated in the pathogenesis of psychiatric disorders, such as schizophrenia, bipolar disorder and major depression. Apoptosis can be mediated by external cell death signals through activation of the initiator caspase-8, which later promotes the activation of caspase-3. The executer caspase-3 has a key role in the apoptotic cell death cascade and modulates synaptic plasticity. Neuronal apoptosis with an increased caspase-3 activity in the cerebral cortex and in the hippocampus was demonstrated in animal models of psychosis. Chronic stress induces depressive-like behavior in rats and was associated with higher level of caspase-3 in the cerebral cortex. Thus, altered caspase-3 activation might trigger synaptic and cellular degeneration in neuropsychiatric disorders. Methods In the present study we investigated postmortem hippocampus and the anterior cingulate cortex using immunohistochemical methods to evaluate the expression of caspase-3 and caspase-8 in postmortem hippocampus and anterior cingulate gyrus tissue specimens in subjects with schizophrenia, bipolar disorder, major depression and matched non-psychiatric control subjects. Results We found that expression levels of caspase-3 were selectively regionally altered in the CA1 subfield of the hippocampus in all three major mental groups. Levels of caspase-3 expression appeared to be lower in subjects with schizophrenia and bipolar disorder compared to control subjects. In major depression the expression level of caspase-3 in the CA1 subfield of the hippocampus was decreased by 57%. However, the mean density of caspase-8 positive neurons was increased by 46% in subjects with bipolar disorder and major depression compared to control. A strong increase caspase-3 expression was found in the anterior cingulate cortex in subjects with schizophrenia by 78% compared to control subjects. No differences across all investigated groups were observed for expression levels of caspase-8 in the anterior cingulate cortex. Conclusion In the present study the apoptotic signaling pathway was found to be altered in the hippocampus and anterior cingulate cortex in schizophrenia, bipolar disorder and major depression.