title: Memory restorative ability of clioquinol in copper-cholesterol-induced experimental dementia in mice.
abstract: BACKGROUND
  Results from various studies indicate that the presence of certain heavy metals such as aluminum (Al), arsenic (As), copper (Cu), lead (Pb), and mercury (Hg) may enhance the aggregation of Aβ and oxidative stress levels leading to neuronal toxicity and Alzheimer's disease (AD). Studies also reveal that anomalous brain copper-cholesterol (Cu-Ch) homeostasis may lead to memory deficits in Swiss albino mice.
  
  
  OBJECTIVE
  The present study investigates the anti-amnesic potential of clioquinol (5-chloro-7-iodoquinolin-8-ol) in cognitive deficits associated with experimental dementia induced by Cu-Ch.
  
  
  METHODS
  Administration of Cu-Ch {0.21 mg/kg, per os - 2% w/v, per os for 8 weeks} was used to induce dementia in Swiss albino mice. The Morris water maze (MWM) test was performed to assess the effect on learning and memory. A battery of biochemical estimations was performed following the MWM test such as brain-reduced glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS), acetylcholinestrase (AChE) activity, and serum cholesterol levels.
  
  
  RESULTS
  Administration of Cu-Ch produced a marked decline in MWM performance measured during the acquisition (78.9 ± 3.3) and retrieval trials (9.5 ± 2.4), reflecting impairment of learning and memory. Cu-Ch-treated mice also exhibited a marked accentuation of AChE activity (5.8 ± 0.55) and TBARS levels (9.74 ± 1.9) along with a decline in the GSH level (15.4 ± 3.3) and the SOD level (26 ± 2.5) when compared with the untreated control group. Administration of clioquinol significantly attenuated Cu-Ch-induced memory deficits and biochemical alterations.
  
  
  CONCLUSIONS
  The findings demonstrate memory restorative ability of clioquinol which may be attributed to its anti-cholinesterase, antioxidative, and cholesterol-lowering potential.
authors: Division of Pharmacology, Chandigarh College of Pharmacy , Landran, Mohali, Punjab , India.
authors: Rohit
authors: R
authors: Mehra
authors: Rupinder K
authors: RK
authors: Sodhi
authors: Neha
authors: N
authors: Aggarwal
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002784:Cholesterol; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D007464:Clioquinol / Q000494:pharmacology*; D003300:Copper; D003704:Dementia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D000077265:Donepezil; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007189:Indans / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D017392:Thiobarbituric Acid Reactive Substances; D003300:Copper; D007464:Clioquinol; D000077265:Donepezil; D002784:Cholesterol; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; C548245:Ache protein, mouse; D005978:Glutathione
keywords: 5-chloro-7-iodoquinolin-8-ol; Alzheimer’s disease; amyloid beta; cognition; neuroprotection