Molecular mechanisms of mood stabilization

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Presentation transcript:

Molecular mechanisms of mood stabilization Galila Agam, PhD Dept. of Clinical Biochemistry and Pharmacology and Psychiatry Research Unit Faculty of Health Sciences Ben-Gurion University of the Negev Beer-Sheva, Israel

Main Mood Stabilizers (antibipolar drugs) + Li+ ion Valproate - CH3 OH O Li+ ion Valproate

Tools Behavioral paradigms - mice KO mice Molecular “Traditional” enzymatic activities Protein levels (WB) mRNA levels (qPCR) Neurochemical metabolism follow-up using radiolabelling Neurogenesis (immunohistochem) DNA microarrays/bioinformatics Behavioral paradigms - mice Mood-related Motor-related Anxiety-related KO mice IMPA1 SMIT1 GSK-3beta

Relevant Lithium-Sensitive Behavioral Paradigms Chronic lithium treatment reduces mice immobility in the Porsolt forced-swim test (FST) (O'Brien et al., 2004; Bersudsky et al., 2007) Lithium attenuates amphetamine-induced hyper-locomotion (Berggren et al., 1978) 5

Heat Map (Z-scores) of 261 genes differentially expressed (p<0.05) IMPA1 KO/Li - frontal cortex CON Li IMPA1 KO CON Li IMPA1 KO Two Gene Groups Below mean Above mean Toker L

Recent areas of interest Neurogenesis Mitochondrial function Autophagy Interest in collaboration Any measurable brain-related parameter