PMID- 23536313
OWN - NLM
STAT- MEDLINE
DCOM- 20131029
LR  - 20211021
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 61
IP  - 6
DP  - 2013 Jun
TI  - Impaired glutamate recycling and GluN2B-mediated neuronal calcium overload in 
      mice lacking TGF-beta1 in the CNS.
PG  - 985-1002
LID - 10.1002/glia.22490 [doi]
AB  - Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine expressed 
      throughout the CNS. Previous studies demonstrated that TGF-beta1 contributes to 
      maintain neuronal survival, but mechanistically this effect is not well 
      understood. We generated a CNS-specific TGF-beta1-deficient mouse model to 
      investigate the functional consequences of TGF-beta1-deficiency in the adult mouse 
      brain. We found that depletion of TGF-beta1 in the CNS resulted in a loss of the 
      astrocyte glutamate transporter (GluT) proteins GLT-1 (EAAT2) and GLAST (EAAT1) 
      and decreased glutamate uptake in the mouse hippocampus. Treatment with TGF-beta1 
      induced the expression of GLAST and GLT-1 in cultured astrocytes and enhanced 
      astroglial glutamate uptake. Similar to GLT-1-deficient mice, 
      CNS-TGF-beta1-deficient mice had reduced brain weight and neuronal loss in the CA1 
      hippocampal region. CNS-TGF-beta1-deficient mice showed GluN2B-dependent aberrant 
      synaptic plasticity in the CA1 area of the hippocampus similar to the glutamate 
      transport inhibitor DL-TBOA and these mice were highly sensitive to excitotoxic 
      injury. In addition, hippocampal neurons from TGF-beta1-deficient mice had elevated 
      GluN2B-mediated calcium signals in response to extrasynaptic glutamate receptor 
      stimulation, whereas cells treated with TGF-beta1 exhibited reduced GluN2B-mediated 
      calcium signals. In summary, our study demonstrates a previously unrecognized 
      function of TGF-beta1 in the CNS to control extracellular glutamate homeostasis and 
      GluN2B-mediated calcium responses in the mouse hippocampus.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Koeglsperger, Thomas
AU  - Koeglsperger T
AD  - Department of Neurology, Center for Neurologic Diseases, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA. 
      thomas.koeglsperger@dzne.lmu.de
FAU - Li, Shaomin
AU  - Li S
FAU - Brenneis, Christian
AU  - Brenneis C
FAU - Saulnier, Jessica L
AU  - Saulnier JL
FAU - Mayo, Lior
AU  - Mayo L
FAU - Carrier, Yijun
AU  - Carrier Y
FAU - Selkoe, Dennis J
AU  - Selkoe DJ
FAU - Weiner, Howard L
AU  - Weiner HL
LA  - eng
GR  - R01 AG043975/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20130328
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Excitatory Amino Acid Transporter 1)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Calcium/*metabolism
MH  - Dendritic Spines/metabolism
MH  - Excitatory Amino Acid Transporter 1/genetics/metabolism
MH  - Excitatory Amino Acid Transporter 2/genetics/metabolism
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synaptic Transmission/physiology
MH  - Transforming Growth Factor beta1/genetics/*metabolism
PMC - PMC3981075
MID - NIHMS562339
EDAT- 2013/03/29 06:00
MHDA- 2013/10/30 06:00
PMCR- 2014/04/09
CRDT- 2013/03/29 06:00
PHST- 2012/04/12 00:00 [received]
PHST- 2013/02/06 00:00 [accepted]
PHST- 2013/03/29 06:00 [entrez]
PHST- 2013/03/29 06:00 [pubmed]
PHST- 2013/10/30 06:00 [medline]
PHST- 2014/04/09 00:00 [pmc-release]
AID - 10.1002/glia.22490 [doi]
PST - ppublish
SO  - Glia. 2013 Jun;61(6):985-1002. doi: 10.1002/glia.22490. Epub 2013 Mar 28.