title: Age-Dependent Effect of β-Amyloid Toxicity on Basal Forebrain Cholinergic Neurons and Inflammation in the Rat Brain.
abstract: Beta-amyloid (Aβ) accumulation, neuroinflammation, basal forebrain cholinergic loss and hippocampal degeneration are well-described pathologies associated with Alzheimer's disease (AD). However, the role that age plays in the susceptibility of the brain to these AD pathologies and the relationships between them is still not well understood. This study investigated the age-related response to intracerebroventricular injection of Aβ(25-35) in 3-, 6- and 9-month-old rats. Aβ toxicity resulted in an age-related increase in cholinergic loss and microglial activation in the basal forebrain along with neuronal loss in the hippocampal CA3 subfield. Performance in the Morris water maze revealed impairments in long-term reference memory in 6-month-old Aβ administered animals, which was not seen in 3-month-old animals. These results support a role of Aβ administration in inducing age-dependent cholinergic loss and neuroinflammation, and additionally provide evidence for a more age-appropriate model of adult-onset Aβ toxicity demonstrating pathological changes that reflect the early stages of AD pathogenesis including neuroinflammation, cholinergic loss and beginning stages of memory impairment.
authors.affiliation: Department of Anatomy & Cell Biology, Western University, London, ON, Canada.
authors.forename: Hayley Joy
authors.initials: HJ
authors.lastname: Nell
authors.affiliation: Department of Anatomy & Cell Biology, Western University, London, ON, Canada.
authors.forename: Shawn Narain
authors.initials: SN
authors.lastname: Whitehead
authors.affiliation: Department of Anatomy & Cell Biology, Western University, London, ON, Canada.
authors.forename: David Floyd
authors.initials: DF
authors.lastname: Cechetto
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D066187:Basal Forebrain / Q000187:drug effects / Q000473:pathology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000473:pathology*; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides
keywords: aging; beta-amyloid; cholinergic loss; neuroinflammation