title: Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat.
abstract: Alzheimer's disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid β oligomers (AβO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AβO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Aβ, microglia, and cholinergic neurons. Rats exposed to AβO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Aβ was only observed in the corpus callosum surrounding the lateral ventricles. AβO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AβO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AβO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.
authors: Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond St, London, ON N6A 5C1, Canada. ryanswong@gmail.com.
authors: Ryan S
authors: RS
authors: Wong
authors: Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond St, London, ON N6A 5C1, Canada. cechetto@uwo.ca.
authors: David F
authors: DF
authors: Cechetto
authors: Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond St, London, ON N6A 5C1, Canada. shawn.whitehead@schulich.uwo.ca.
authors: Shawn N
authors: SN
authors: Whitehead
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments
keywords: Alzheimer’s disease; amyloid β oligomers; behavioural deficits; cholinergic neuron depletion; microglial activation