| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
(1) The expression of Fos protein was examined within various brain structures in allylnitrile-, crotononitrile-, and vehicle-treated mice. In each nitrile-treated mouse, Fos expression was observed in brain structures, which were divided into two groups. The structures in group 1 showed Fos expression between 1.5 h and 2 days postdosings, and in those in group 2 expression remained for up to 30 days postdosing. The results indicate that each nitrile induces Fos expression by causing a change in the peripheral vestibular system, resulting in behavioral abnormalities.
(2) Five neuronal markers, γ-aminobutyric acid (GABA), tyrosine hydroxylase, serotorain, the serotonin transporter and choline acetyltransferase were immunohistochemically examined within various brain structures in allylnitrile and vehicle-treated mice. Allylnitrile induced changes in the immunolabelling of GABA in the medial habenula, interpedunculat nucleus, substantia nigra, dorsal raphe nucleus and median raphe nucleus. The results suggest that the GABA ergic systems through the medial habenula-interpeduncular nucleus-ascending rap he nuclei relay and through the substantia nigra may be involved in allylnitrile-induced behavioral abnormalities.
2.Apoptotic pathway in allylnitrile-treated PC12 cells
Treatment of differentiated PC12 cells with 5 mM allylnitrile (for up to 12 h) caused nuclear condensation and DNA fragmentation. Allylnitrile-induced apoptosis could be inhibited with the caspase inhibitor. Allylnitrile induced a time-dependentincrease in caspase-3 activity in differentiated cells. Caspase-3 cleavage, cytochromec release from mitochondria and poly (ADP-ribose) polymerase degradation were observed during allylnitrile-induced apoptosis. The results indicate that allylnitrile induces apoptosis through cytochrome c-caspase-3 path way in differentiated PC12 cells.
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