| First Author | Turnbull MT | Year | 2018 |
| Journal | Front Mol Neurosci | Volume | 11 |
| Pages | 51 | PubMed ID | 29520217 |
| Mgi Jnum | J:289791 | Mgi Id | MGI:6433887 |
| Doi | 10.3389/fnmol.2018.00051 | Citation | Turnbull MT, et al. (2018) Acute Down-regulation of BDNF Signaling Does Not Replicate Exacerbated Amyloid-beta Levels and Cognitive Impairment Induced by Cholinergic Basal Forebrain Lesion. Front Mol Neurosci 11:51 |
| abstractText | Degeneration of basal forebrain cholinergic neurons (BFCNs) precedes hippocampal degeneration and pathological amyloid-beta (Abeta) 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 Abeta 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 Abeta 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 Abeta nor caused cognitive deficits. These results suggest that the cognitive decline and Abeta pathology induced by BFCN loss occur independent of dysfunctional neuronal BDNF signaling, and may therefore be directly underpinned by reduced cholinergic neurotransmission. |
