Journal
NEUROBIOLOGY OF AGING
Volume 117, Issue -, Pages 24-32Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2022.03.017
Keywords
Basal forebrain; Cholinergic neurons; MRI; Volumetry; Morphometry; Medial septum; Alzheimer?s disease
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Funding
- National Health and Medical Research Council (NHMRC) [GNT1162505]
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Degeneration of cholinergic neurons in the basal forebrain (BF) is a contributing factor to cognitive impairment. However, the volume changes measured by structural MRI in the BF do not directly reflect the changes in cholinergic neurons.
Degeneration of cholinergic neurons in the basal forebrain (BF) contributes to cognitive impairment in Alzheimer's disease (AD) and other disorders. Atrophy of BF volume measured by structural MRI is thought to represent the loss of cholinergic neurons in this structure. As there are multiple types of neurons in the BF as well as glia and axons, whether this MRI measure actually reflects the change of cholinergic neurons has not been verified. In this study, we assessed BF cholinergic neuron number by histological counts and compared with the volume measurements by in vivo MRI in 3xTg mice, a model of familial AD. Both manual and template-based segmentation revealed atrophy of the medial septum (MS), consistent with a significant reduction in cholinergic neuron number. However, MRI-measured volume reduction did not correlate with the reduced cholinergic neuron number. To directly test whether specific loss of cholinergic neurons results in BF atrophy, we selectively ablated the cholinergic neurons in the MS. However, no detectable change in MRI volume was observed between lesioned and unlesioned mice. The results indicate that although loss of cholinergic neurons within the BF likely contributes to volume loss, this volume change cannot be taken as a direct biomarker of cholinergic neuron number.(c) 2022 Elsevier Inc. All rights reserved.
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