title: Possible role of metal ionophore against zinc induced cognitive dysfunction in D-galactose senescent mice.
abstract: Metal ionophores are considered as potential anti-dementia agents, and some are currently undergoing clinical trials. Many metals are known to accumulate and distribute abnormally in the aging brain. Alterations in zinc metal homeostasis in the glutaminergic synapse could contribute to ageing and the pathophysiology of Alzheimer's disease (AD). The present study was designed to investigate the effect of metal ionophores on long term administration of zinc in D-galactose induced senescent mice. The ageing model was established by combined administration of zinc and D-galactose to mice for 6 weeks. A novel metal ionophore, PBT-2 was given daily to zinc-induced d-galactose senescent mice. The cognitive behaviour of mice was monitored using the Morris Water Maze. The anti-oxidant status and amyloidogenic activity in the ageing mouse was measured by determining mito-oxidative parameters and deposition of amyloid β (Aβ) in the brain. Systemic administration of both zinc and D-galactose significantly produced memory deficits, mito-oxidative damage, heightened acetylcholinesterase enzymatic activity and deposition of amyloid-β. Treatment with PBT-2 significantly improved behavioural deficits, biochemical profiles, cellular damage, and curbed the deposition of APP in zinc-induced senescent mice. These findings suggest that PBT-2, acting as a metal protein attenuating compound, may be helpful in the prevention of AD or alleviation of ageing.
authors.affiliation: Department of Pharmacology, ISF College of Pharmacy, Ghalkalan, Moga, 142-001, Punjab, India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Bharti
authors.affiliation: Brain Degeneration and Therapeutics Group, Pharmaceutical & Life Sciences Community of Research (CoRe), UniversitiTeknologi MARA (UiTM), 40450, Shah Alam, Selangor, Malaysia.|Brain Research Laboratory, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Abu Bakar Abdul
authors.initials: AB
authors.lastname: Majeed
authors.affiliation: Department of Pharmacology, ISF College of Pharmacy, Ghalkalan, Moga, 142-001, Punjab, India. atishprakash@gmail.com.|Brain Degeneration and Therapeutics Group, Pharmaceutical & Life Sciences Community of Research (CoRe), UniversitiTeknologi MARA (UiTM), 40450, Shah Alam, Selangor, Malaysia. atishprakash@gmail.com.|Brain Research Laboratory, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor, Malaysia. atishprakash@gmail.com.
authors.forename: Atish
authors.initials: A
authors.lastname: Prakash
mesh_terms: D000284:Administration, Oral; D000375:Aging; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry; D000818:Animals; D007464:Clioquinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005690:Galactose / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019287:Zinc Sulfate / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; C531955:PBT2 compound; D019287:Zinc Sulfate; D007464:Clioquinol; D005690:Galactose
keywords: Ageing; Metal ionophore; Mitochondrial dysfunction; Oxidative stress; Zinc