Acute Down-regulation of BDNF Signaling Does Not Replicate Exacerbated Amyloid-beta Levels and Cognitive Impairment Induced by Cholinergic Basal Forebrain Lesion

Turnbull, Marion T., Boskovic, Zoran and Coulson, Elizabeth J. (2018) Acute Down-regulation of BDNF Signaling Does Not Replicate Exacerbated Amyloid-beta Levels and Cognitive Impairment Induced by Cholinergic Basal Forebrain Lesion. Frontiers in Molecular Neuroscience, 11 1-13. doi:10.3389/fnmol.2018.00051


Author Turnbull, Marion T.
Boskovic, Zoran
Coulson, Elizabeth J.
Title Acute Down-regulation of BDNF Signaling Does Not Replicate Exacerbated Amyloid-beta Levels and Cognitive Impairment Induced by Cholinergic Basal Forebrain Lesion
Journal name Frontiers in Molecular Neuroscience   Check publisher's open access policy
ISSN 1662-5099
Publication date 2018-02-22
Year available 2018
Sub-type Article (original research)
DOI 10.3389/fnmol.2018.00051
Open Access Status DOI
Volume 11
Start page 1
End page 13
Total pages 13
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Language eng
Subject 1312 Molecular Biology
2804 Cellular and Molecular Neuroscience
Abstract Degeneration of basal forebrain cholinergic neurons (BFCNs) precedes hippocampal degeneration and pathological amyloid-beta (A beta) accumulation, and underpins the development of cognitive dysfunction in sporadic Alzheimer's disease(AD). We hypothesized that degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, which in turn promotes the development of A beta pathology and cognitive impairment. Here we show that lesion of septo-hippocampal BFCNs in a pre-symptomatic transgenic amyloid AD mouse model (APP/PS1 mice) increases soluble A beta levels in the hippocampus, and induces cognitive deficits in a spatial memory task that are not seen in either unlesioned APP/PS1 or non-transgenic littermate control mice. Furthermore, the BFCN lesion results in decreased levels of brain-derived neurotrophic factor (BDNF). However, viral knockdown of neuronal BDNF in the hippocampus of APP/PS1 mice (in the absence of BFCN loss) neither increased the level of A beta nor caused cognitive deficits. These results suggest that the cognitive decline and A beta pathology induced by BFCN loss occur independent of dysfunctional neuronal BDNF signaling, and may therefore be directly underpinned by reduced cholinergic neurotransmission.
Keyword Messenger-Rna Regulation
Alzheimers-Disease
Neurotrophic Factor
A-Beta
Tau-Protein
In-Vivo
Mice
Brain
Atrophy
Degeneration
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
School of Biomedical Sciences Publications
 
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Created: Sat, 10 Mar 2018, 20:12:51 EST