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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
O
CH3 CH2 CH2
CH C OH
CH3 CH2 CH2
Valproate
Tools
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 hyperlocomotion (Berggren et al., 1978)
Heat Map (Z-scores) of 261 genes differentially expressed (p<0.05)
IMPA1 KO/Li - frontal cortex
CON
Li
IMPA1 KO
Two Gene Groups
CON
Below mean
Above mean
Li
IMPA1 KO
Toker L
Recent areas of interest
• Neurogenesis
• Mitochondrial function
• Autophagy
Interest in collaboration
Any measurable brain-related parameter