Effect of anti-dementia drugs on LPS induced neuroinflammation in mice.
Inflammation has been recently implicated in pathogenesis of dementia disorders. Effect of anti-dementia (Acetylcholinesterase inhibitor) drugs tacrine, rivastigmine and donepezil were studied on neuroinflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) in mice. Interleukin-2 (IL-2) and isoforms of acetylcholinesterase (AChE) were estimated in different brain areas as marker for neuroinflammation and cholinergic activity respectively. LPS significantly increased the level of IL-2 in all the brain areas while enhancement of AChE activity varied in brain areas. It was found that administration of tacrine, rivastigmine and donepezil in mice significantly attenuated the LPS induced increased levels of IL-2 along with the significant reduction of AChE activity predominantly in salt soluble (SS) fraction as compared to the detergent soluble (DS) fraction in a dose dependent manner. In vitro effect of LPS was also studied in different brain areas. LPS significantly increased the AChE activity in SS fractions but the significant increase was not found in DS fractions. The present study indicate that cholinesterase inhibitor anti-dementia drugs are effective against LPS induced neuroinflammation that may be linked to enhanced cholinergic activity.
Tyagi
Ethika
E
Division of Pharmacology, Central Drug Research Institute, Lucknow 226001, India.
Agrawal
Rahul
R
Nath
Chandishwar
C
Shukla
Rakesh
R
D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003704:Dementia / Q000188:drug therapy*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D000068836:Rivastigmine; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D007189:Indans; D007376:Interleukin-2; D008070:Lipopolysaccharides; D048448:Phenylcarbamates; D010880:Piperidines; D013619:Tacrine; D000077265:Donepezil; D000110:Acetylcholinesterase; D000068836:Rivastigmine