KASHIWA Atsushi TOKYO MEDICAL & DENTAL UNIVERSITY, GRADUATE SCHOOL, ASSISTANT, 大学院・医歯学総合研究科, 助手 (10301227)
NISHIKAWA Toru TOKYO MEDICAL & DENTAL UNIVERSITY, GRADUATE SCHOOL, PROFESSOR, 大学院・医歯学総合研究科, 教授 (00198441)
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¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
We examined effects of FG 7142 (20 mg/kg, I.p.), an axiogenic stressor, on c-Fos-like immunoreactivity in the rat brain. In the forebrain of 56-day-old rats, the drug induced a dense nuclear c-Fos immunostaining in the piriform cortex, cingulate and retosplenial cortex, layers II-IV of the neocortex, lateral habenula, lateral sepum, striatum, central and medial nucleus of the amygdala, but a sparse c-Fos immunostaining in the hippocampus and layer I of the neocortex. Among these regions, 8-day-old rats expressed much fewer c-Fos-positive cells in the cingulate and retosplenial cortex, neocortex, lateral habenular, lateral septum and medial nucleus amygdala than young adult rats after the FG 7142 administration. These difference in the regional distribution of a neural activity marker, c-Fos, could reflect the postnatal developmental of neuronal populations or neuron circuits involved in stress response and/or anxiety in the brain.
To determine the genes responsible for stress or anxiety state in the brain of rodents, transcriptional changes in the cerebral cortex after the FG 7142 injection were rnonitered using DNA microarray. In the young adult rodents, a number of genes, such as c-fos and CYR 61, were significantly changed in the transcriptional levels. However, no changes in the levels in the cortex were observed in any of genes examined in the array in 8-day- old rodents. Thus, the gene exhibited age-dependent changes in the transcriptional levels following FG 7142 could play an important role in the neuonal circuits of stress response and/or anxiety state in the brain.