RGD Reference Report - Possible role of propofol's cyclooxygenase-inhibiting property in alleviating dopaminergic neuronal loss in the substantia nigra in an MPTP-induced murine model of Parkinson's disease.

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Possible role of propofol's cyclooxygenase-inhibiting property in alleviating dopaminergic neuronal loss in the substantia nigra in an MPTP-induced murine model of Parkinson's disease.
Authors:	Kubo, K Inada, T Shingu, K
Citation:	Kubo K, etal., Brain Res. 2011 Apr 28;1387:125-33. Epub 2011 Mar 2.
RGD ID:	5508224
Pubmed:	PMID:21376018 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.brainres.2011.02.079 (Journal Full-text)
Propofol is an intravenous anesthetic widely used for sedation and general anesthesia. We investigated the effect of propofol on prostanoid production by activated microglia. Primary microglial culture was obtained from the brains of neonatal C57BL/6 mice. The microglia were stimulated with lipopolysaccharide (LPS) in the presence of propofol. Propofol suppressed the LPS-induced production of prostaglandin E(2) and thromboxane B(2). Cyclooxygenase (COX) protein expression and arachidonic acid release were not affected by propofol, while COX enzyme activity was significantly inhibited by propofol. The COX-inhibiting activity was also observed with purified enzymes, with COX-2 inhibition being significantly greater than COX-1 inhibition. Next, we studied whether the COX-inhibiting activity of propofol resulted in dopaminergic neuroprotection in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease, in which COX inhibitors, such as non-steroidal anti-inflammatory drugs, are reported to be neuroprotective. C57BL/6 mice received intraperitoneal injections of MPTP with or without propofol treatment, and the dopaminergic neurons in the substantia nigra pars compacta (SNpc) were examined immunohistochemically by observing the tyrosine hydroxylase-positive cells. The number of dopaminergic neurons in the SNpc was significantly reduced by MPTP treatment, while the MPTP-induced neuronal loss was minimal upon treatment with propofol or the selective COX-2 inhibitor, NS-398. These results indicate that propofol might be beneficial in mitigating MPTP-induced dopaminergic neurons, possibly via its COX-inhibiting activity.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PTGS2	Human	Parkinsonism		ISO	Ptgs2 (Mus musculus)		RGD
Ptgs2	Rat	Parkinsonism		ISO	Ptgs2 (Mus musculus)		RGD
Ptgs2	Mouse	Parkinsonism		IMP			RGD

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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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Possible role of propofol's cyclooxygenase-inhibiting property in alleviating dopaminergic neuronal loss in the substantia nigra in an MPTP-induced murine model of Parkinson's disease.