Dorit Ben-Shachar, PhD
MSc, 1979 - Technion - Israel Institute of Technology, Haifa
PhD, 1985 - Technion - Israel Institute of Technology, Haifa
Mitochondrial and molecular mechanisms and their translation to behavioral responses in psychiatric disorders
Psychiatric disorders are a diverse group of brain disorders with symptoms that primarily involve emotion, high cognitive functions, and the ability to control complex behaviors. Unlike many neurological disorders, the common psychiatric disorders appear to engage widely distributed neural networks. In our laboratory, we use different experimental models to study biochemical and molecular processes in psychiatric-related behavioral abnormalities, and the mechanism of action of psychotropic treatments. These range from human brain studies, animal studies, and the use of neuronal cells and human lymphocytes.
Two main research projects illustrate our research interests:
Mitochondria and schizophrenia: Mitochondria play a key role in synaptic potentiation and neurotransmission as well as in morphogenesis and plasticity of synapses. All are important for optimal functioning of critical circuits necessary for normal cognitive, emotional and behavioral functions. The research in our laboratory focuses on mitochondrial function in schizophrenia as compared to major depression and bipolar disorder. We investigate the mechanism of the abnormalities that are observed in the mitochondria at the functional and molecular levels, and its possible link to dopamine and the transcription factor Sp1.
Stress-related pathologies: Neuronal plasticity has been implicated in major depression and its treatment. The prevailing hypothesis suggests that glucocorticoids (stress signal) are detrimental to neuronal plasticity, while antidepressants, as well as monoamines, are able to reconstitute this plasticity. We focus on the interaction between stress hormones and monoamines or antidepressant drugs by studying the effects of such an interaction on behavioral responses, brain area-dependent alterations in plasticity relevant genes, DNA methylation, and intracellular signaling pathways.
Ben-Shachar, D., Karry, R. 2008. Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS ONE 3, e3676.
Brenner-Lavie, H., Klein, E., Zuk, R., Gazawi, H., Ljubuncic, P., Ben-Shachar, D. 2008. Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: Relevance to dopamine pathology in schizophrenia. Biochim Biophys Acta 1777, 173-185.
Ben-Shachar, D., Karry, R. 2007. Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. PLoS ONE 2, e817.