title: Effects of naproxen on immune responses in a colchicine-induced rat model of Alzheimer's disease.
abstract: BACKGROUND
  The components of the immune system have been indicated to be linked with the neurotoxicity in Alzheimer's disease (AD). The participation of the immune system in the neurodegeneration in a rat model of colchicine-induced AD has not been explored.
  
  
  METHODS
  In the present study, hippocampal neurodegeneration along with reactive oxygen species (ROS), nitrite and TNF-α in the hippocampus and some systemic immune responses were measured after 15 and 21 days of intracerebroventricular colchicine injection in rats and again after oral administration of different doses of the anti-inflammatory drug naproxen in AD rats.
  
  
  RESULTS
  Chromatolysis and amyloid plaques were found along with higher ROS, nitrite and TNF-α levels in the hippocampus of colchicine-induced AD rats, and these changes were prevented by naproxen in a dose-dependent manner. Alterations in immunological parameters [increased phagocytic activity of white blood cells and splenic polymorphonuclear cells (PMN), increased cytotoxicity and decreased leucocyte adhesive inhibition index (LAI) of splenic mononuclear cells (MNC)] were also observed in colchicine-injected rats, which showed a dose-dependent recovery after oral administration of naproxen in AD rats. The number of plaques, chromatolysis of Nissl granules, TNF-α, nitrite and ROS levels in the hippocampus, phagocytic activity of splenic PMN and LAI of splenic MNC in AD rats showed greater changes in the 21- than in the 15-day study, and the recovery of these parameters after administration of naproxen differed between the two study durations.
  
  
  CONCLUSIONS
  The present study shows that colchicine-induced neurodegeneration is time dependent and mediated by cyclooxygenase-induced neuroinflammation, which is reflected in the systemic immunological responses.
authors.affiliation: Neurophysiology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, India.
authors.forename: Susmita
authors.initials: S
authors.lastname: Sil
authors.forename: Ananda Raj
authors.initials: AR
authors.lastname: Goswami
authors.forename: Goutam
authors.initials: G
authors.lastname: Dutta
authors.forename: Tusharkanti
authors.initials: T
authors.lastname: Ghosh
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003078:Colchicine / Q000633:toxicity*; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D006854:Hydrocortisone / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009288:Naproxen / Q000627:therapeutic use*; D009573:Nitrites / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects; D058225:Plaque, Amyloid / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D050257:Tubulin Modulators / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D009573:Nitrites; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; D009288:Naproxen; D003078:Colchicine; D006854:Hydrocortisone