title: Co-morbid beta-amyloid toxicity and stroke produce impairments in an ambiguous context task in rats without any impairment in spatial working memory.
abstract: Sporadic Alzheimer's disease (AD) accounts for a high proportion of AD cases. Therefore, it is of importance to investigate other factors that contribute to the etiology and progression of AD. AD is characterized by decreased cholinergic tone, tau hyperphosphorylation and beta-amyloid (Aβ) accumulation. In addition to the hallmark pathology, other factors have been identified that increase the risk of AD, including stroke. This study examined the combined effects of beta-amyloid administration and unilateral stroke in an animal model of AD. Adult rats were given a sham surgery, bilateral intraventricular infusion of 10 μL of 50n mol Aβ(25-35), a unilateral injection of endothelin-1 into the right striatum, or Aβ and endothelin-1 administration in combination. Following a recovery period, rats were tested in the 1-trial place learning variant of the Morris water task followed by an ambiguous discriminative fear-conditioning to context task. After behavioural assessment, rats were euthanized, and representative sections of the medial septum were analyzed for differences in choline-acetyltransferase (ChAT) immunohistochemistry. No differences were observed in spatial working memory, but the combined effect of Aβ and stroke resulted in deficits in the discriminative fear-conditioning to context task. A trend towards decreased ChAT-positive staining in the medial septum was observed. This study indicates that Aβ and stroke in combination produce worse functional consequences than when experienced alone, furthering the concept of AD as a disease with multiple and complex etiologies.
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada. Electronic address: rj.keeley@uleth.ca.
authors.forename: R J
authors.initials: RJ
authors.lastname: Keeley
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada.
authors.forename: N S
authors.initials: NS
authors.lastname: Hong
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Fisher
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: McDonald
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000633:toxicity; D005239:Fear / Q000187:drug effects / Q000502:physiology; D057967:Infusions, Intraventricular; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology*; D020521:Stroke / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*
chemical_list: D016229:Amyloid beta-Peptides; D019332:Endothelin-1; D002795:Choline O-Acetyltransferase
keywords: Acetylcholine; Alzheimer’s disease (AD); Beta-amyloid; Cue ambiguity; Discriminative fear-conditioning to context; Hippocampus; Morris water task; Stroke