PMID- 24360280
OWN - NLM
STAT- MEDLINE
DCOM- 20140226
LR  - 20230207
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 155
IP  - 7
DP  - 2013 Dec 19
TI  - Microglia promote learning-dependent synapse formation through brain-derived 
      neurotrophic factor.
PG  - 1596-609
LID - S0092-8674(13)01481-5 [pii]
LID - 10.1016/j.cell.2013.11.030 [doi]
AB  - Microglia are the resident macrophages of the CNS, and their functions have been 
      extensively studied in various brain pathologies. The physiological roles of 
      microglia in brain plasticity and function, however, remain unclear. To address 
      this question, we generated CX3CR1(CreER) mice expressing tamoxifen-inducible Cre 
      recombinase that allow for specific manipulation of gene function in microglia. 
      Using CX3CR1(CreER) to drive diphtheria toxin receptor expression in microglia, 
      we found that microglia could be specifically depleted from the brain upon 
      diphtheria toxin administration. Mice depleted of microglia showed deficits in 
      multiple learning tasks and a significant reduction in motor-learning-dependent 
      synapse formation. Furthermore, Cre-dependent removal of brain-derived 
      neurotrophic factor (BDNF) from microglia largely recapitulated the effects of 
      microglia depletion. Microglial BDNF increases neuronal tropomyosin-related 
      kinase receptor B phosphorylation, a key mediator of synaptic plasticity. 
      Together, our findings reveal that microglia serve important physiological 
      functions in learning and memory by promoting learning-related synapse formation 
      through BDNF signaling.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Parkhurst, Christopher N
AU  - Parkhurst CN
AD  - Molecular Neurobiology Program, The Kimmel Center for Biology and Medicine at the 
      Skirball Institute, Department of Neuroscience and Physiology, New York 
      University School of Medicine, New York, NY 10016, USA.
FAU - Yang, Guang
AU  - Yang G
AD  - Department of Anesthesiology, New York University School of Medicine, New York, 
      NY 10016, USA.
FAU - Ninan, Ipe
AU  - Ninan I
AD  - Department of Psychiatry, New York University School of Medicine, New York, NY 
      10016, USA.
FAU - Savas, Jeffrey N
AU  - Savas JN
AD  - Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 
      92037, USA.
FAU - Yates, John R 3rd
AU  - Yates JR 3rd
AD  - Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 
      92037, USA.
FAU - Lafaille, Juan J
AU  - Lafaille JJ
AD  - Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine at the 
      Skirball Institute, Department of Pathology, New York University School of 
      Medicine, New York, NY 10016, USA.
FAU - Hempstead, Barbara L
AU  - Hempstead BL
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Littman, Dan R
AU  - Littman DR
AD  - Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine at the 
      Skirball Institute, Department of Pathology, New York University School of 
      Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York 
      University School of Medicine, New York, NY 10016, USA.
FAU - Gan, Wen-Biao
AU  - Gan WB
AD  - Molecular Neurobiology Program, The Kimmel Center for Biology and Medicine at the 
      Skirball Institute, Department of Neuroscience and Physiology, New York 
      University School of Medicine, New York, NY 10016, USA. Electronic address: 
      wenbiao.gan@nyumc.org.
LA  - eng
GR  - R01 MH067880/MH/NIMH NIH HHS/United States
GR  - R01 NS047325/NS/NINDS NIH HHS/United States
GR  - R01 NS030687/NS/NINDS NIH HHS/United States
GR  - R01 NS087198/NS/NINDS NIH HHS/United States
GR  - R01 MH096899/MH/NIMH NIH HHS/United States
GR  - NS030687/NS/NINDS NIH HHS/United States
GR  - F30 MH096370/MH/NIMH NIH HHS/United States
GR  - P01 NS074972/NS/NINDS NIH HHS/United States
GR  - P41 GM103533/GM/NIGMS NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - R01 MH96899/MH/NIMH NIH HHS/United States
GR  - P01 AG031097/AG/NIA NIH HHS/United States
GR  - R56 MH096899/MH/NIMH NIH HHS/United States
GR  - F32 AG039127/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CX3C Chemokine Receptor 1)
RN  - 0 (Cx3cr1 protein, mouse)
RN  - 0 (Receptors, Chemokine)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
CIN - Nat Rev Neurosci. 2014 Feb;15(2):69. PMID: 24434913
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - CX3C Chemokine Receptor 1
MH  - Gene Expression
MH  - Learning/*physiology
MH  - Mice
MH  - Microglia/cytology/*physiology
MH  - Neuronal Plasticity
MH  - Protein Kinases/metabolism
MH  - Receptors, Chemokine/genetics/metabolism
MH  - Signal Transduction
MH  - *Synapses
PMC - PMC4033691
MID - NIHMS580679
EDAT- 2013/12/24 06:00
MHDA- 2014/02/27 06:00
PMCR- 2014/05/26
CRDT- 2013/12/24 06:00
PHST- 2013/06/24 00:00 [received]
PHST- 2013/09/25 00:00 [revised]
PHST- 2013/11/20 00:00 [accepted]
PHST- 2013/12/24 06:00 [entrez]
PHST- 2013/12/24 06:00 [pubmed]
PHST- 2014/02/27 06:00 [medline]
PHST- 2014/05/26 00:00 [pmc-release]
AID - S0092-8674(13)01481-5 [pii]
AID - 10.1016/j.cell.2013.11.030 [doi]
PST - ppublish
SO  - Cell. 2013 Dec 19;155(7):1596-609. doi: 10.1016/j.cell.2013.11.030.