title: Memory restorative role of statins in experimental dementia: an evidence of their cholesterol dependent and independent actions.
abstract: The study was aimed at investigating the effects of pitavastatin, simvastatin (lipophilic statins) and fluvastatin (hydrophilic statin) on memory deficits associated with Alzheimer's type dementia in mice. Dementia was induced with chronic administration of a high fat diet (HFD) or intracebroventricular streptozotocin (icv STZ, two doses of 3 mg/kg) in separate groups of animals. Memory of the animals was assessed by the Morris water maze (MWM) test. Brain thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels were measured to assess total oxidative stress. Brain acetylcholinesterase (AChE) activity and total serum cholesterol levels were also measured. Icv STZ or HFD produced a significant impairment of learning and memory. Higher levels of brain AChE activity and TBARS and lower levels of GSH were observed in icv STZ- as well as HFD-treated animals. HFD-treated mice also showed a significant increase in total serum cholesterol levels. Pitavastatin and simvastatin each significantly attenuated STZ-induced memory deficits and biochemical changes; however, fluvastatin produced no significant effect on icv STZ-induced dementia or biochemical levels. Administration of any one of the three statins not only lowered HFD-induced rise in total serum cholesterol level but also attenuated HFD-induced memory deficits. Further pitavastatin and simvastatin administration also reversed HFD-induced changes in biochemicals level, while fluvastatin failed to produce any significant effect. This study demonstrates the potential of statins in memory dysfunctions associated with experimental dementia and provides evidence of their cholesterol-dependent and -independent actions.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala (Punjab), PIN-147002, India.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Dalla
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
authors.forename: Dhandeep
authors.initials: D
authors.lastname: Singh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D003704:Dementia / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use; D000077340:Fluvastatin; D005978:Glutathione / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D013311:Streptozocin; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011804:Quinolines; D017392:Thiobarbituric Acid Reactive Substances; D000077340:Fluvastatin; D013311:Streptozocin; D002784:Cholesterol; D019821:Simvastatin; D000110:Acetylcholinesterase; D005978:Glutathione; C108475:pitavastatin