title: 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.
authors: Neurophysiology laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700 009, West Bengal, India. Electronic address: sil.susmitasil@gmail.com.
authors: Susmita
authors: S
authors: Sil
authors: Neurophysiology laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700 009, West Bengal, India. Electronic address: tusharkantighosh53@yahoo.in.
authors: Tusharkanti
authors: T
authors: Ghosh
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications*; D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology*; D003078:Colchicine / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology*; D000077613:Etoricoxib; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology*; D058225:Plaque, Amyloid / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D013450:Sulfones / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D011725:Pyridines; D013450:Sulfones; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D003078:Colchicine; D000077613:Etoricoxib
keywords: Colchicine; Cox-2; Memory; Neurodegeneration; Neuroinflammation; PGE(2)