RGD Reference Report - Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy: effect of nimesulide.

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Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy: effect of nimesulide.
Authors:	Gu, B Desjardins, P Butterworth, RF
Citation:	Gu B, etal., Metab Brain Dis. 2008 Jun;23(2):175-87. Epub 2008 May 15.
RGD ID:	2300278
Pubmed:	PMID:18481165 (View Abstract at PubMed)
DOI:	DOI:10.1007/s11011-008-9089-2 (Journal Full-text)
Thiamine deficiency (TD) in both humans and experimental animals results in severe mitochondrial dysfunction and leads to selective neuronal cell death in diencephalic and cerebellar structures. We have investigated cyclooxygenase-2 (COX-2) expression in vulnerable (medial thalamus, inferior colliculus) and spared (frontal cortex) regions of rats with thiamine deficiency. Expression of COX-2 mRNA was selectively increased (twofold, p < 0.001) in vulnerable regions at symptomatic stages of encephalopathy (14 days) of TD compared to pair-fed controls or presymptomatic (days 12) rats. Induction of COX-2 expression was accompanied by a significant increase (two- to threefold, p < 0.001) in prostanglandin E2 (PGE2) synthesis in vulnerable regions at symptomatic stages of TD. COX-2 immunolabeling revealed a neuronal localization and COX-2 immunoreactive neurons were significantly increased at symptomatic stages of encephalopathy. Administration of nimesulide, a highly specific COX-2 inhibitor, significantly reduced PGE-2 levels in vulnerable regions but, rather than being neuroprotective, precipitated encephalopathy and exacerbated neuronal cell death due to TD. These findings suggest that newly synthesized prostanoids exert a neuroprotective role in TD.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PTGS2	Human	Wernicke encephalopathy		ISO	Ptgs2 (Rattus norvegicus)	mRNA more ...	RGD
Ptgs2	Rat	Wernicke encephalopathy		IMP		mRNA more ...	RGD
Ptgs2	Mouse	Wernicke encephalopathy		ISO	Ptgs2 (Rattus norvegicus)	mRNA more ...	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ptgs2 (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)

Ptgs2 (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)

PTGS2 (prostaglandin-endoperoxide synthase 2)

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Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy: effect of nimesulide.