Temporospatial patterns of COX-2 expression and pyramidal cell degeneration in the rat hippocampus after trimethyltin administration |
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Authors: | Shirakawa Takafumi Nakano Kenji Hachiya Naomi S Kato Nobumasa Kaneko Kiyotoshi |
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Affiliation: | Drug Discovery Research, Drug Safety Research Labs, Astellas Pharma Inc., 1-1-8 Azusawa, Itabashi-ku, Tokyo 174-8511, Japan. takafumi.shirakawa@jp.astellas.com |
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Abstract: | The temporospatial profile of cyclooxygenase-2 (COX-2) expression and neuronal degeneration following trimethyltin (TMT) administration was investigated in the rat hippocampus region. In the CA1 region, significant COX-2 expression was detected on day 3 after TMT administration but pyramidal cell degeneration was detected only on day 5 and thereafter. In the CA3 region, on the other hand, the constitutive COX-2 expression remained unchanged, and more severe pyramidal cell degeneration started on day 3. Concomitant with these observations, we observed that the coadministration of a COX-2 inhibitor prevented such neuronal degeneration only in the CA1 region and not in the CA3 region. In addition, COX-2 inhibition did not affect the increase in the plasma corticosterone concentration after TMT administration. Furthermore, the COX-2 inhibitor did not alleviate TMT-induced locomotor hyperactivity in rats, for which inhibitors of corticosterone synthesis are known to be effective. These data suggest that the COX-2-dependent pathway appears to assist TMT-induced degeneration of CA1 pyramidal cells but not CA3 pyramidal cells in a corticosterone-independent manner. |
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