title: Aluminum-Induced Cholinergic Deficits in Different Brain Parts and Its Implications on Sociability and Cognitive Functions in Mouse.
abstract: Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer's disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl3(250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication.
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan.
authors.forename: Syeda Mehpara
authors.initials: SM
authors.lastname: Farhat
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan.
authors.forename: Aamra
authors.initials: A
authors.lastname: Mahboob
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan.
authors.forename: Ghazala
authors.initials: G
authors.lastname: Iqbal
authors.affiliation: Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan. touqeer.aahmed@gmail.com.
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D003072:Cognition Disorders / Q000139:chemically induced*; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D021641:Recognition, Psychology / Q000187:drug effects*; D012919:Social Behavior
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride; D000109:Acetylcholine
keywords: Acetylcholine; Choline acetyltransferase gene expression; Free choline; Novel object recognition; Social novelty preference