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Spatial memory impairment in mice with immunotoxic lesions of the cholinergic basal forebrain
Author(s) -
Wrenn Craige Charles,
Schaapveld Caitlin Marie,
Bennett Nick,
Bansal Sonia,
Willoughby Christy,
Peterson Joel,
Krogh Kelly,
Wolfe Brady,
Hidding Jennifer
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.847.7
Subject(s) - basal forebrain , cholinergic neuron , cholinergic , saporin , morris water navigation task , forebrain , neuroscience , latency (audio) , saline , barnes maze , psychology , medicine , endocrinology , pathology , cognition , central nervous system , immunology , spatial learning , electrical engineering , immunotoxin , antibody , monoclonal antibody , engineering
Degeneration of the cholinergic basal forebrain (CBF) is a feature of Alzheimer's disease (AD) that correlates with dementia severity. This correlation has motivated investigators to develop animal models of AD by lesioning the CBF. We tested the hypothesis that mu‐p75‐saporin creates cholinergic lesions in mice and that these lesions result in deficits in spatial cognition. C57BL/6J mice received intraventricular injection of either a high (4 μg) or low (2 μg) dose of mu‐p75‐saporin and were tested in the Morris water maze. Mice receiving 4 μg showed increased latency to find the hidden platform during training. This increased latency was confounded by motor deficits because impairments in swim speed were observed. In a probe trial, mice receiving 4 μg swam a greater average distance from the platform location than saline‐treated mice. Mice receiving 2 μg showed increased latency to find the platform with no confounding effect on swim speed. In a probe trial, mice receiving 2 μg swam with similar proximity to the platform location as saline‐treated mice. Staining of the brains for acetylcholinesterase, p75, and parvalbumin showed that the treated animals had specific lesions of the CBF. In summary, features of Alzheimer's disease can be modeled in mice using mu‐p75‐ saporin, but higher doses produce confounds in motor ability.