PMID- 30098276
OWN - NLM
STAT- MEDLINE
DCOM- 20191004
LR  - 20200225
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Print)
IS  - 1050-9631 (Linking)
VI  - 28
IP  - 12
DP  - 2018 Dec
TI  - Hippocampal brain-derived neurotrophic factor determines recruitment of 
      anatomically connected networks after stress in diabetic mice.
PG  - 900-912
LID - 10.1002/hipo.23018 [doi]
AB  - 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.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Wosiski-Kuhn, Marlena
AU  - Wosiski-Kuhn M
AD  - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 
      Augusta University, Augusta, Georgia.
FAU - Bota, Mihail
AU  - Bota M
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
FAU - Snider, Christina A
AU  - Snider CA
AD  - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 
      Augusta University, Augusta, Georgia.
FAU - Wilson, Steven P
AU  - Wilson SP
AD  - Department of Pharmacology, Physiology, and Neuroscience, University of South 
      Carolina School of Medicine, Columbia, South Carolina.
FAU - Venkataraju, Kannan U
AU  - Venkataraju KU
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
FAU - Osten, Pavel
AU  - Osten P
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
FAU - Stranahan, Alexis M
AU  - Stranahan AM
AUID- ORCID: 0000-0003-0612-2837
AD  - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 
      Augusta University, Augusta, Georgia.
LA  - eng
GR  - K01 DK100616/DK/NIDDK NIH HHS/United States
GR  - R01 DK110586/DK/NIDDK NIH HHS/United States
GR  - R03 DK101817/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181106
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Anxiety/metabolism
MH  - Behavior, Animal
MH  - *Brain Mapping
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corticosterone/blood
MH  - Diabetes Mellitus, Experimental/*physiopathology
MH  - Feedback, Physiological
MH  - Genes, Immediate-Early
MH  - Genes, fos
MH  - Hippocampus/physiopathology
MH  - Hypothalamo-Hypophyseal System/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Pituitary-Adrenal System/*metabolism
MH  - Septal Nuclei/physiopathology
MH  - Stress, Psychological/*metabolism
PMC - PMC6544163
MID - NIHMS992893
OTO - NOTNLM
OT  - BDNF
OT  - BNST
OT  - HPA axis
OT  - anxiety
OT  - iDISCO
EDAT- 2018/08/12 06:00
MHDA- 2019/10/08 06:00
PMCR- 2019/12/01
CRDT- 2018/08/12 06:00
PHST- 2018/05/26 00:00 [received]
PHST- 2018/07/18 00:00 [revised]
PHST- 2018/08/01 00:00 [accepted]
PHST- 2018/08/12 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2018/08/12 06:00 [entrez]
PHST- 2019/12/01 00:00 [pmc-release]
AID - 10.1002/hipo.23018 [doi]
PST - ppublish
SO  - Hippocampus. 2018 Dec;28(12):900-912. doi: 10.1002/hipo.23018. Epub 2018 Nov 6.