Temporospatial patterns of COX-2 expression and pyramidal cell degeneration in the rat hippocampus after trimethyltin administration.
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.
Shirakawa
Takafumi
T
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
Nakano
Kenji
K
Hachiya
Naomi S
NS
Kato
Nobumasa
N
Kaneko
Kiyotoshi
K
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000097:blood; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004660:Encephalitis / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D005452:Fluoresceins; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D009930:Organic Chemicals; D017966:Pyramidal Cells / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000633:toxicity*
D052246:Cyclooxygenase 2 Inhibitors; D005452:Fluoresceins; D009930:Organic Chemicals; D011725:Pyridines; D014298:Trimethyltin Compounds; C435731:fluoro jade; C046488:trimethyltin; C013109:metapyrone; D051546:Cyclooxygenase 2; D003345:Corticosterone