PMID- 22542678 OWN - NLM STAT- MEDLINE DCOM- 20130401 LR - 20211021 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 212 DP - 2012 Jun 14 TI - Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior. PG - 1-18 LID - 10.1016/j.neuroscience.2012.03.031 [doi] AB - Brain-derived neurotrophic factor (BDNF) plays important roles in the development, maintenance, and plasticity of the mammalian forebrain. These functions include regulation of neuronal maturation and survival, axonal and dendritic arborization, synaptic efficacy, and modulation of complex behaviors including depression and spatial learning. Although analysis of mutant mice has helped establish essential developmental functions for BDNF, its requirement in the adult is less well documented. We have studied late-onset forebrain-specific BDNF knockout (CaMK-BDNF(KO)) mice, in which BDNF is lost primarily from the cortex and hippocampus in early adulthood, well after BDNF expression has begun in these structures. We found that although CaMK-BDNF(KO) mice grew at a normal rate and can survive more than a year, they had smaller brains than wild-type siblings. The CaMK-BDNF(KO) mice had generally normal behavior in tests for ataxia and anxiety, but displayed reduced spatial learning ability in the Morris water task and increased depression in the Porsolt swim test. These behavioral deficits were very similar to those we previously described in an early-onset forebrain-specific BDNF knockout. To identify an anatomical correlate of the abnormal behavior, we quantified dendritic spines in cortical neurons. The spine density of CaMK-BDNF(KO) mice was normal at P35, but by P84, there was a 30% reduction in spine density. The strong similarities we find between early- and late-onset BDNF knockouts suggest that BDNF signaling is required continuously in the CNS for the maintenance of some forebrain circuitry also affected by developmental BDNF depletion. CI - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Vigers, A J AU - Vigers AJ AD - Department of Molecular, Cellular, and Developmental Biology, 347 UCB, University of Colorado, Boulder, CO 80309, USA. vigers@colorado.edu FAU - Amin, D S AU - Amin DS FAU - Talley-Farnham, T AU - Talley-Farnham T FAU - Gorski, J A AU - Gorski JA FAU - Xu, B AU - Xu B FAU - Jones, K R AU - Jones KR LA - eng GR - NS-P01-16033/NS/NINDS NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - KO1-NS01872/NS/NINDS NIH HHS/United States GR - EY014998/EY/NEI NIH HHS/United States GR - R01 EY014998/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120425 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Behavior, Animal/physiology MH - Brain-Derived Neurotrophic Factor/*biosynthesis/deficiency/genetics MH - Cerebral Cortex/*growth & development/*metabolism MH - Dendritic Spines/*metabolism/pathology MH - Developmental Disabilities/genetics/*metabolism/physiopathology MH - Disease Models, Animal MH - Female MH - Male MH - Mental Disorders/genetics/*metabolism/physiopathology MH - Mice MH - Mice, Knockout MH - Mice, Transgenic PMC - PMC4880414 MID - NIHMS373150 COIS- There are no actual or potential conflicts of interest for any of the authors. EDAT- 2012/05/01 06:00 MHDA- 2013/04/02 06:00 PMCR- 2016/05/25 CRDT- 2012/05/01 06:00 PHST- 2011/11/16 00:00 [received] PHST- 2012/03/23 00:00 [revised] PHST- 2012/03/26 00:00 [accepted] PHST- 2012/05/01 06:00 [entrez] PHST- 2012/05/01 06:00 [pubmed] PHST- 2013/04/02 06:00 [medline] PHST- 2016/05/25 00:00 [pmc-release] AID - S0306-4522(12)00293-X [pii] AID - 10.1016/j.neuroscience.2012.03.031 [doi] PST - ppublish SO - Neuroscience. 2012 Jun 14;212:1-18. doi: 10.1016/j.neuroscience.2012.03.031. Epub 2012 Apr 25.