PMID- 22832656
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20220309
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 1
IP  - 9
DP  - 2011 Sep 13
TI  - Enriched environment treatment reverses depression-like behavior and restores 
      reduced hippocampal neurogenesis and protein levels of brain-derived neurotrophic 
      factor in mice lacking its expression through promoter IV.
PG  - e40
LID - 10.1038/tp.2011.33 [doi]
AB  - Promoter IV-driven expression of brain-derived neurotrophic factor (BDNF), a 
      major neuronal growth factor, is implicated in the pathophysiology of major 
      depression. We previously reported that mice lacking expression of BDNF through 
      promoter IV (BDNF-KIV mice) exhibit a depression-like phenotype. Here, we 
      examined whether the depression-like phenotype and decreased levels of BDNF 
      because of promoter IV deficit could be rescued by enriched environment (EE) 
      treatment, a potential antidepressant intervention. Three weeks of EE treatment 
      rescued depression-like behavior of BDNF-KIV mice as assessed by the tail 
      suspension test, open-field test and sucrose preference test. EE treatment also 
      increased BDNF transcripts driven by multiple endogenous promoters and restored 
      BDNF protein levels in the hippocampus (HIP) of BDNF-KIV mice. Further, we 
      investigated adult hippocampal neurogenesis as a possible cellular mechanism 
      underlying the depression-like behavior and its recovery in BDNF-KIV mice. We 
      found that the number of surviving progenitors and their dendritic length in the 
      dentate gyrus of the HIP were reduced in BDNF-KIV mice compared with the control 
      wild-type mice. EE treatment restored the reduction in cell survival and 
      dendritic length and increased cell proliferation in BDNF-KIV mice. In 
      conclusion, this study demonstrated that EE rescued depression-like behavior, 
      decreased BDNF levels and defective neurogenesis in the HIP caused by lack of 
      promoter IV-driven BDNF expression. These results suggest that decreased BDNF 
      levels because of one impaired promoter can be compensated by other BDNF 
      promoters and that BDNF levels may be one of the key factors regulating 
      depression and antidepressant effects through hippocampal neurogenesis.
FAU - Jha, S
AU  - Jha S
AD  - Department of Pharmacology, University of Tennessee Health Science Center, 
      Memphis, TN 38163, USA.
FAU - Dong, B
AU  - Dong B
FAU - Sakata, K
AU  - Sakata K
LA  - eng
PT  - Journal Article
DEP - 20110913
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*physiology
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/deficiency/genetics
MH  - Depression/genetics/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Hippocampus/*growth & development/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Mutant Strains
MH  - Neurogenesis/*genetics
MH  - Promoter Regions, Genetic/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Treatment Outcome
PMC - PMC3309483
EDAT- 2011/01/01 00:00
MHDA- 2013/04/05 06:00
PMCR- 2011/09/01
CRDT- 2012/07/27 06:00
PHST- 2012/07/27 06:00 [entrez]
PHST- 2011/01/01 00:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - tp201133 [pii]
AID - 10.1038/tp.2011.33 [doi]
PST - epublish
SO  - Transl Psychiatry. 2011 Sep 13;1(9):e40. doi: 10.1038/tp.2011.33.