title: Subtle learning and memory impairment in an idiopathic rat model of Alzheimer's disease utilizing cholinergic depletions and β-amyloid.
abstract: Alzheimer's disease (AD) is a disease of complex etiology, involving multiple risk factors. When these risk factors are presented concomitantly, cognition and brain pathology are more severely compromised than if those risk factors were presented in isolation. Reduced cholinergic tone and elevated amyloid-beta (Aβ) load are pathological hallmarks of AD. The present study sought to investigate brain pathology and alterations in learning and memory when these two factors were presented together in rats. Rats received either sham surgeries, cholinergic depletions of the medial septum, intracerebroventricular Aβ25-35 injections, or both cholinergic depletion and Aβ25-35 injections (Aβ+ACh group). The Aβ+ACh rats were unimpaired in a striatal dependent visual discrimination task, but had impaired acquisition in the standard version of the Morris water task. However, these rats displayed normal Morris water task retention and no impairment in acquisition of a novel platform location during a single massed training session. Aβ+ACh rats did not have exacerbated brain pathology as indicated by activated astroglia, activated microglia, or accumulation of Aβ. These data suggest that cholinergic depletions and Aβ injections elicit subtle cognitive deficits when behavioural testing is conducted shortly after the presentation of these factors. These factors might have altered hippocampal synaptic plasticity and thus resemble early AD pathology.
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada. Electronic address: deibel@uleth.ca.
authors.forename: S H
authors.initials: SH
authors.lastname: Deibel
authors.affiliation: Vulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Weishaupt
authors.affiliation: Vulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, Ontario, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Regis
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada.
authors.forename: N S
authors.initials: NS
authors.lastname: Hong
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: Keeley
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: Balog
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Bye
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Himmler
authors.affiliation: Vulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, Ontario, Canada.
authors.forename: S N
authors.initials: SN
authors.lastname: Whitehead
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Alberta, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: McDonald
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000008:administration & dosage; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D007858:Learning / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage; D000076985:Saporins; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism
chemical_list: C085696:192 IgG-saporin; D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D010446:Peptide Fragments; D054789:Ribosome Inactivating Proteins, Type 1; C074636:amyloid beta-protein (25-35); D002795:Choline O-Acetyltransferase; D000076985:Saporins; D000109:Acetylcholine
keywords: Alzheimer's disease; Cholinergic depletions; Cofactor theory; Hippocampus; Rat; β-amyloid