title: Nitric oxide synthase inhibitor, aminoguanidine reduces intracerebroventricular colchicine induced neurodegeneration, memory impairments and changes of systemic immune responses in rats.
abstract: Intracerebroventricular (i.c.v.) injection of colchicine induces neurodegeneration, memory impairments and changes of some systemic immune responses in rats. Though the role of cox 2 in these colchicine induced changes have been evaluated, the influence of nitric oxide synthase (NOS) remains to be studied. The present study was designed to assess the role of NOS on the i.c.v. colchicine induced neurodegeneration, memory impairments and changes of some systemic immune responses by inhibiting its activity with aminoguanidine. In the present study the impairments of working and reference memories, neurodegeneration (chromatolysis and plaque formation) and changes of neuroinflammatory markers in the hippocampus (increased TNF α, IL 1β, ROS and nitrite) along with changes of serum inflammatory markers (TNF α, IL 1β, ROS and nitrite) and alteration of systemic immune responses (higher phagocytic activity of blood WBC and splenic PMN, higher cytotoxicity and lower leukocyte adhesion inhibition index of splenic MNC) were measured in the intracerebroventricular colchicine injected rats (ICIR). Administration of aminoguanidine (p.o. 30/50mg/kg body weight) to ICIR resulted in recovery of neuroinflammation and partial prevention of neurodegeneration which could be corroborated with the partial recovery of memory impairments in this model. The recovery of serum inflammatory markers and the systemic immune responses in ICIR was also observed after administration of aminoguanidine. Therefore, the present study shows that aminoguanidine can protect the colchicine induced neurodegeneration, memory impairments, and changes of systemic immune systemic responses in ICIR by inhibiting the iNOS.
authors.affiliation: 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.
authors.forename: Susmita
authors.initials: S
authors.lastname: Sil
authors.affiliation: 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.forename: Tusharkanti
authors.initials: T
authors.lastname: Ghosh
authors.affiliation: 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.
authors.forename: Rupsa
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: 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.
authors.forename: Pritha
authors.initials: P
authors.lastname: Gupta
mesh_terms: D000818:Animals; D003078:Colchicine / Q000008:administration & dosage / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000276:immunology; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D003078:Colchicine
keywords: Aminoguanidine; Colchicine; Neurodegeneration; Neuroinflammation; Systemic immune responses