Hippocampal brain-derived neurotrophic factor determines recruitment of anatomically connected networks after stress in diabetic mice

Wosiski-Kuhn, M., Bota, M., Snider, C. A., Wilson, S. P., Venkataraju, K. U., Osten, P., Stranahan, A. M. (August 2018) Hippocampal brain-derived neurotrophic factor determines recruitment of anatomically connected networks after stress in diabetic mice. Hippocampus, 28 (12). pp. 900-912. ISSN 1050-9631

URL: https://www.ncbi.nlm.nih.gov/pubmed/30098276
DOI: 10.1002/hipo.23018


Diabetes increases adrenal steroids in humans and animal models, but potential interactions with psychological stress remain poorly understood. Diabetic rodents exhibit anxiety and reductions in hippocampal brain-derived neurotrophic factor (BDNF) expression, and these studies investigated whether loss of BDNF-driven hippocampal activity promotes anxiety and disinhibits the HPA axis. Mice with genetic obesity and diabetes (db/db) received intrahippocampal injections of lentivirus for BDNF overexpression (db/db-BDNFOE), and Wt mice received lentiviral constructs for BDNF knockdown (Wt-BDNFKD). Behavioral anxiety, and glucocorticoid responses to acute restraint were compared with mice that received a fluorescent reporter (Wt-GFP, db/db-GFP). These experiments revealed that changes in hippocampal BDNF were necessary and sufficient for behavioral anxiety and HPA axis disinhibition. To examine patterns of stress-induced regional activity, we used algorithmic detection of cFos and automated segmentation of forebrain regions to generate maps of functional covariance, which were subsequently aligned with anatomical connectivity weights from the Brain Architecture Management database. db/db-GFP mice exhibited reduced activation of the hippocampal ventral subiculum (vSub) and anterior bed nucleus of stria terminalis (aBNST), and increases in the paraventricular hypothalamus (PVH), relative to Wt-GFP. BDNFKD recapitulated this pattern in Wt mice, and BDNFOE normalized activation of the vSub>aBNST>PVH pathway in db/db mice. Analysis of forebrain activation revealed largely overlapping patterns of network disruption in db/db-GFP and Wt-BDNFKD mice, implicating BDNF-driven hippocampal activity as a determinant of stress vulnerability in both the intact and diabetic brain. This article is protected by copyright. All rights reserved.

Item Type: Paper
Subjects: diseases & disorders > nutritional and metabolic diseases > diabetes
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
diseases & disorders > nutritional and metabolic diseases > obesity
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: Matthew Dunn
Date: 11 August 2018
Date Deposited: 15 Aug 2018 15:32
Last Modified: 18 Oct 2019 18:50
PMCID: PMC6544163
Related URLs:
URI: https://repository.cshl.edu/id/eprint/37105

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