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

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.