POSTER
USE OF LASER CAPTURE
MICRODISSECTION TECHNOLOGY TO IDENTIFY DRUG- AND DISEASE-ASSOCIATED GENE
EXPRESSION CHANGES IN HIPPOCAMPAL NEURONS
Vinod
Charles and Jeffrey Brockman
Psychiatric Genomics, Inc., Gaithersburg MD, 20878
Brain
imaging studies have revealed structural and functional alterations in several
brain areas in schizophrenia, most prominently in the temporal lobe,
hippocampus, and frontal cortex. We describe methods whereby Hippocampal
neurons were obtained using laser-capture microdissection (LCM) from the Stanley
Neuropathology Consortium (schizophrenia, bipolar disease, major depressive
disorder and normal controls). Agilent cDNA microarrays revealed decreases in
the expression of many genes in the dentate gyrus in schizophrenia relative to
bipolar disorder, major depression, and controls. These changes were
independent of medication history, post-mortem interval, or a variety of other
factors. Many of these gene changes were also replicated in a separate
schizophrenia cohort. The most pronounced decreases included genes involved in
a synaptic transmission, vesicular transport and neurite outgrowth. Many of
these same genes were also decreased in CA3 pyramidal neurons, the target of
dentate granule cells, with little change in bipolar disorder and depression.
The decreased expression of genes involved in synaptic transmission in the
hippocampus may contribute to the limbic and affective deficits seen in
schizophrenia.