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. 2016 Feb 15:291:115-24.
doi: 10.1016/j.jneuroim.2015.12.003. Epub 2015 Dec 11.

Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer's Disease

Susmita Sil  1 , Tusharkanti Ghosh  2
Affiliations

Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer's Disease

Susmita Sil et al. J Neuroimmunol. .

Abstract

The neurodegeneration in colchicine induced AD (cAD) rats is linked with neuroinflammation. The inducible cox-2 present in the brain may participate in the neuroinflammatory process related to progressive neurodegeneration in cAD rats. The aim of this study is to investigate the role of cox-2 in the neurodegeneration and cognitive impairments in cAD rats. The parameters of memory (working and reference memory), inflammatory markers [IL-1β, TNF-α, prostaglandin E2 (PGE2), cox-2 level] and histopathology of hippocampus were measured after 21-day of i.c.v. colchicine injection in rats and compared with that of control and sham operated rats. These parameters were also measured in these 3 different groups of rats after p.o. administration of 3 different doses of etoricoxib, a cox 2 inhibitor. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus and increased cox-2 and PGE2 levels in hippocampus in cAD. Administration of etoricoxib in cAD rats resulted in recovery of memory impairments, neurodegeneration and neuroinflammation in hippocampus and inhibition of cox-2 and PGE2 levels in hippocampus. It appears from the results that activation of cox-2 in cAD is related to neuroinflammation involved in neurodegeneration. Colchicine induced initial neurodegeneration may trigger cascade of events for a progressive neurodegeneration where cox-2 activation plays a critical role. Moreover, this cox-2 mediated neurodegeneration is related to impairments of memory parameters. Thus, the present study showed that the impairments of memory and neurodegeneration in the hippocampus of cAD in 21-day study are mediated by cox-2 induced neuroinflammation.

Keywords: Colchicine; Cox-2; Memory; Neurodegeneration; Neuroinflammation; PGE(2).

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