RGD Reference Report - Suppressing inflammatory cascade by cyclo-oxygenase inhibitors attenuates quinolinic acid induced Huntington's disease-like alterations in rats. - Rat Genome Database

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Suppressing inflammatory cascade by cyclo-oxygenase inhibitors attenuates quinolinic acid induced Huntington's disease-like alterations in rats.

Authors: Kalonia, H  Kumar, A 
Citation: Kalonia H and Kumar A, Life Sci. 2011 Apr 25;88(17-18):784-91. Epub 2011 Feb 26.
RGD ID: 5508227
Pubmed: PMID:21362433   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2011.02.020   (Journal Full-text)

AIMS: The aim of this study was to investigate the protective effects of cyclo-oxygenase inhibitors against quinolinic acid (QA) induced Huntington's disease-like alterations in rats. MAIN METHODS: Quinolinic acid (300 nmol) was administered intrastriatally into the striatum to induce Huntington's disease-like alteration. Cyclo-oxygenase inhibitors celecoxib (15 and 30 mg/kg) and meloxicam (10 and 20mg/kg) were given for 21 days. In behavioral assessment locomotor, rotarod, and balance beam walk performances were assessed. Oxidative stress, mitochondrial dysfunction, proinflammatory cytokines and caspase-3 were assessed on day 21 after behavioral assessments. KEY FINDINGS: Intrastriatal quinolinic acid (300 nmol) administration significantly altered the body weight, motor coordination, and induced oxidative damage (as indicated by the increase in lipid peroxidation and nitrite concentration) in the striatum as compared to sham group. Besides quinolinic acid (300 nmol) significantly depleted the mitochondrial enzyme complex levels and increased TNF-alpha, IL-6 and caspase-3 (marker of apoptotic cell death) levels in the striatum. Chronic treatment with celecoxib (15 and 30 mg/kg) significantly attenuated the quinolinic acid-induced behavioral and biochemical alterations, while meloxicam was able to reverse behavioral alterations at higher dose (20 mg/kg) as compared to the quinolinic acid treated group. Chronic treatment with the selective COX-2 inhibitors significantly restored the mitochondrial enzyme complex activities as well as attenuated TNF-alpha, IL-6 and caspase-3 levels as compared to the quinolinic acid treated group. SIGNIFICANCE: Results of the present study demonstrate the protective effect of cyclo-oxygenase inhibitors in the experimental models of Huntington's disease; and further provide evidence toward the involvement of neuroinflammatory cascade in the pathogenesis of Huntington's disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGS2HumanHuntington's disease  ISOPtgs2 (Rattus norvegicus) RGD 
Ptgs2RatHuntington's disease  IMP  RGD 
Ptgs2MouseHuntington's disease  ISOPtgs2 (Rattus norvegicus) 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)

Objects referenced in this article
Gene Ptgs1 prostaglandin-endoperoxide synthase 1 Rattus norvegicus

Additional Information