PMID- 23082852
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20130121
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Linking)
VI  - 12
IP  - 1
DP  - 2013 Feb
TI  - NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic 
      factor-induced facilitation of hippocampal synaptic transmission in a Tau 
      transgenic model.
PG  - 11-23
LID - 10.1111/acel.12018 [doi]
AB  - While the spatiotemporal development of Tau pathology has been correlated with 
      occurrence of cognitive deficits in Alzheimer's patients, mechanisms underlying 
      these deficits remain unclear. Both brain-derived neurotrophic factor (BDNF) and 
      its tyrosine kinase receptor TrkB play a critical role in hippocampus-dependent 
      synaptic plasticity and memory. When applied on hippocampal slices, BDNF is able 
      to enhance AMPA receptor-dependent hippocampal basal synaptic transmission 
      through a mechanism involving TrkB and N-methyl-d-Aspartate receptors (NMDAR). 
      Using THY-Tau22 transgenic mice, we demonstrated that hippocampal Tau pathology 
      is associated with loss of synaptic enhancement normally induced by exogenous 
      BDNF. This defective response was concomitant to significant memory impairments. 
      We show here that loss of BDNF response was due to impaired NMDAR function. 
      Indeed, we observed a significant reduction of NMDA-induced field excitatory 
      postsynaptic potential depression in the hippocampus of Tau mice together with a 
      reduced phosphorylation of NR2B at the Y1472, known to be critical for NMDAR 
      function. Interestingly, we found that both NR2B and Src, one of the NR2B main 
      kinases, interact with Tau and are mislocalized to the insoluble protein fraction 
      rich in pathological Tau species. Defective response to BDNF was thus likely 
      related to abnormal interaction of Src and NR2B with Tau in THY-Tau22 animals. 
      These are the first data demonstrating a relationship between Tau pathology and 
      synaptic effects of BDNF and supporting a contribution of defective BDNF response 
      and impaired NMDAR function to the cognitive deficits associated with 
      Tauopathies.
CI  - (c) 2012 The Authors Aging Cell (c) 2012 Blackwell Publishing Ltd/Anatomical Society 
      of Great Britain and Ireland.
FAU - Burnouf, Sylvie
AU  - Burnouf S
AD  - Universite Lille-Nord de France, UDSL, F-59045, Lille Cedex, France.
FAU - Martire, Alberto
AU  - Martire A
FAU - Derisbourg, Maxime
AU  - Derisbourg M
FAU - Laurent, Cyril
AU  - Laurent C
FAU - Belarbi, Karim
AU  - Belarbi K
FAU - Leboucher, Antoine
AU  - Leboucher A
FAU - Fernandez-Gomez, Francisco J
AU  - Fernandez-Gomez FJ
FAU - Troquier, Laetitia
AU  - Troquier L
FAU - Eddarkaoui, Sabiha
AU  - Eddarkaoui S
FAU - Grosjean, Marie-Eve
AU  - Grosjean ME
FAU - Demeyer, Dominique
AU  - Demeyer D
FAU - Muhr-Tailleux, Anne
AU  - Muhr-Tailleux A
FAU - Buisson, Alain
AU  - Buisson A
FAU - Sergeant, Nicolas
AU  - Sergeant N
FAU - Hamdane, Malika
AU  - Hamdane M
FAU - Humez, Sandrine
AU  - Humez S
FAU - Popoli, Patrizia
AU  - Popoli P
FAU - Buee, Luc
AU  - Buee L
FAU - Blum, David
AU  - Blum D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121123
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/genetics/*metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Disease Models, Animal
MH  - Hippocampus/drug effects/metabolism/*physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synaptic Transmission/drug effects/*physiology
MH  - Transgenes
MH  - tau Proteins/biosynthesis/*genetics
EDAT- 2012/10/23 06:00
MHDA- 2013/10/01 06:00
CRDT- 2012/10/23 06:00
PHST- 2012/09/20 00:00 [accepted]
PHST- 2012/10/23 06:00 [entrez]
PHST- 2012/10/23 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
AID - 10.1111/acel.12018 [doi]
PST - ppublish
SO  - Aging Cell. 2013 Feb;12(1):11-23. doi: 10.1111/acel.12018. Epub 2012 Nov 23.