GENE EXPRESSION CHANGES FOLLOWING NEONATAL VENTRAL HIPPOCAMPAL LESIONS

GENE EXPRESSION CHANGES FOLLOWING

NEONATAL VENTRAL HIPPOCAMPAL LESIONS

G.K. Wood, E.R. Marcotte, R. Quirion,

L.K. Srivastava

Psychiatry, Douglas Hospital Research

Center, McGill University, Montreal PQ, Canada

Neonatal excitotoxic lesions of the rat

ventral hippocampus (VH) have previously been demonstrated to induce behavioral

and pharmacological abnormalities analogous to those observed in

schizophrenia.  In particular, these animals display postpubertal emergence

of altered dopamine-mediated behaviors that are reflected of increased NAc

sensitivity to DA agonists and reduced prefrontal dopamine downregulation of

locomotion.  To better characterize the neurochemical substrates underlying

these alterations, we have used DNA microarrays to examine gene expression

profiles in the adult PFC and NAc of neonatally VH lesioned rats.  RNA was

extracted from pooled micropunched samples of 12-15 rats and reverse transcribed

to make 32P-labelled cDNA probes that were hybridized to identical

membranes containing 1,176 known rat genes (Atlas Array, Clontech).  Three

main clusters of altered gene transcripts showing up to 6 fold changes were

detected, involving synaptic terminal proteins, cAMP-dependent signal

transduction elements, and Ca2+ binding proteins.  These findings support

the critical role of various signal transduction pathways in mediating some of

the behavioral and biochemical changes observed in this animal model.

Slides: