Regulation of GAP-43 expression by chronic desipramine treatment in rat cultured hippocampal cells.
BACKGROUND
The importance of molecular and cellular changes in hippocampus in major depression and in the mechanism of action of antidepressants has become increasingly clear. Identification of novel targets for antidepressants in hippocampus is important to understanding their therapeutic effects.


METHODS
We used cDNA microarray to measure the expression patterns of multiple genes in primary cultured rat hippocampal cells. In situ hybridization and Northern and immunoblotting analysis were used to determine brain regional distribution and mRNA and protein levels of target genes.


RESULTS
After comparing hybridized signals between control and desipramine treated groups, we found that chronic treatment with desipramine increased the expression of six genes and decreased the expression of two genes. One of the upregulated genes is growth associated protein GAP-43. In situ hybridization revealed that desipramine increased GAP-43 gene expression in dentate gyrus but not other brain regions. Northern and immunoblotting analysis revealed that desipramine increased GAP-43 mRNA and protein levels. GAP-43 expression is also increased by another antidepressant, tranylcypromine, but not by lithium or haloperidol.


CONCLUSIONS
Because GAP-43 regulates growth of axons and modulates the formation of new connections, our findings suggest that desipramine may have an effect on neuronal plasticity in the central nervous system.
Chen
Biao
B
Department of Psychiatry, McMaster University, Hamilton, Canada.
Wang
Jun Feng
JF
Sun
Xiujun
X
Young
L Trevor
LT
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D015152:Blotting, Northern; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D003891:Desipramine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D019922:GAP-43 Protein / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D000929:Antidepressive Agents, Tricyclic; D018076:DNA, Complementary; D019922:GAP-43 Protein; D003891:Desipramine