PMID- 28324222
OWN - NLM
STAT- MEDLINE
DCOM- 20190221
LR  - 20190221
IS  - 1863-2661 (Electronic)
IS  - 1863-2653 (Print)
IS  - 1863-2653 (Linking)
VI  - 222
IP  - 7
DP  - 2017 Sep
TI  - Bdnf mRNA splice variants differentially impact CA1 and CA3 dendrite complexity 
      and spine morphology in the hippocampus.
PG  - 3295-3307
LID - 10.1007/s00429-017-1405-3 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is an activity-dependent neurotrophin 
      critical for neuronal plasticity in the hippocampus. BDNF is encoded by multiple 
      transcripts with alternative 5' untranslated regions (5'UTRS) that display 
      activity-induced targeting to distinct subcellular compartments. While individual 
      Bdnf 5'UTR transcripts influence dendrite morphology in cultured hippocampal 
      neurons, it is unknown whether Bdnf splice variants impact dendrite arborization 
      in functional classes of neurons in the intact hippocampus. Moreover, the 
      contribution of Bdnf 5'UTR splice variants to dendritic spine density and shape 
      has not been explored. We analyzed the structure of CA1 and CA3 dendrite arbors 
      in transgenic mice lacking BDNF production from exon (Ex) 1, 2, 4, or 6 splice 
      variants (Bdnf-e1, -e2, -e4, and -e6(-/-) mice) and found that loss of BDNF from 
      individual Bdnf mRNA variants differentially impacts the complexity of apical and 
      basal arbors in vivo. Consistent with the subcellular localization studies, Bdnf 
      Ex2 and Ex6 transcripts significantly contributed to dendrite morphology in both 
      CA1 and CA3 neurons. While Bdnf-e2(-/-) mice showed increased branching proximal 
      to the soma in CA1 and CA3 apical arbors, Bdnf-e6(-/-) mice showed decreased 
      apical and basal dendrite complexity. Analysis of spine morphology on 
      Bdnf-e6(-/-) CA1 dendrites revealed changes in the percentage of differently 
      sized spines on apical, but not basal, branches. These results provide further 
      evidence that Bdnf splice variants generate a spatial code that mediates the 
      local actions of BDNF in distinct dendritic compartments on structural and 
      functional plasticity.
FAU - Maynard, Kristen R
AU  - Maynard KR
AD  - Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 855 North 
      Wolfe Street, Suite 300, Baltimore, MD, 21205, USA.
FAU - Hobbs, John W
AU  - Hobbs JW
AD  - Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 855 North 
      Wolfe Street, Suite 300, Baltimore, MD, 21205, USA.
FAU - Sukumar, Mahima
AU  - Sukumar M
AD  - Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 855 North 
      Wolfe Street, Suite 300, Baltimore, MD, 21205, USA.
FAU - Kardian, Alisha S
AU  - Kardian AS
AD  - Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 855 North 
      Wolfe Street, Suite 300, Baltimore, MD, 21205, USA.
FAU - Jimenez, Dennisse V
AU  - Jimenez DV
AD  - Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 855 North 
      Wolfe Street, Suite 300, Baltimore, MD, 21205, USA.
FAU - Schloesser, Robert J
AU  - Schloesser RJ
AD  - Sheppard-Pratt Lieber Research Institute, Baltimore, MD, 21204, USA.
FAU - Martinowich, Keri
AU  - Martinowich K
AUID- ORCID: 0000-0003-0031-8468
AD  - Lieber Institute for Brain Development, Johns Hopkins Medical Campus, 855 North 
      Wolfe Street, Suite 300, Baltimore, MD, 21205, USA. keri.martinowich@libd.org.
AD  - Departments of Psychiatry & Behavioral Sciences, and Neuroscience, Johns Hopkins 
      University School of Medicine, Baltimore, MD, 21205, USA. 
      keri.martinowich@libd.org.
LA  - eng
GR  - R01 MH105592/MH/NIMH NIH HHS/United States
GR  - T32 MH015330/MH/NIMH NIH HHS/United States
GR  - T32MH01533037/National Institute of Mental Health/
GR  - RO1MH105592/National Institute of Mental Health/
PT  - Journal Article
DEP - 20170321
PL  - Germany
TA  - Brain Struct Funct
JT  - Brain structure & function
JID - 101282001
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - CA1 Region, Hippocampal/*cytology
MH  - CA3 Region, Hippocampal/*cytology
MH  - Dendrites/*metabolism
MH  - Dendritic Spines/metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Image Processing, Computer-Assisted
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Confocal
MH  - Neurons/*cytology
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/*genetics
PMC - PMC5608635
MID - NIHMS861883
OTO - NOTNLM
OT  - BDNF transcripts
OT  - Dendrite branching
OT  - Hippocampus
OT  - Spatial code
OT  - Spine morphology
COIS- Conflict of interest The authors declare that they have no conflict of interest.
EDAT- 2017/03/23 06:00
MHDA- 2019/02/23 06:00
PMCR- 2018/09/01
CRDT- 2017/03/22 06:00
PHST- 2016/11/21 00:00 [received]
PHST- 2017/03/13 00:00 [accepted]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2019/02/23 06:00 [medline]
PHST- 2017/03/22 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - 10.1007/s00429-017-1405-3 [pii]
AID - 10.1007/s00429-017-1405-3 [doi]
PST - ppublish
SO  - Brain Struct Funct. 2017 Sep;222(7):3295-3307. doi: 10.1007/s00429-017-1405-3. 
      Epub 2017 Mar 21.