PMID- 17442827
OWN - NLM
STAT- MEDLINE
DCOM- 20070507
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 16
DP  - 2007 Apr 18
TI  - Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in 
      mouse model of Huntington's disease.
PG  - 4424-34
AB  - Asymptomatic Huntington's disease (HD) patients exhibit memory and cognition 
      deficits that generally worsen with age. Similarly, long-term potentiation (LTP), 
      a form of synaptic plasticity involved in memory encoding, is impaired in HD 
      mouse models well before motor disturbances occur. The reasons why LTP 
      deteriorates are unknown. Here we show that LTP is impaired in hippocampal slices 
      from presymptomatic Hdh(Q92) and Hdh(Q111) knock-in mice, describe two factors 
      contributing to this deficit, and establish that potentiation can be rescued with 
      brain-derived neurotrophic factor (BDNF). Baseline physiological measures were 
      unaffected by the HD mutation, but LTP induction and, to a greater degree, 
      consolidation were both defective. The facilitation of burst responses that 
      normally occurs during a theta stimulation train was reduced in HD knock-in mice, 
      as was theta-induced actin polymerization in dendritic spines. The decrease in 
      actin polymerization and deficits in LTP stabilization were reversed by BDNF, 
      concentrations of which were substantially reduced in hippocampus of both 
      Hdh(Q92) and Hdh(Q111) mice. These results suggest that the HD mutation 
      discretely disrupts processes needed to both induce and stabilize LTP, with the 
      latter effect likely arising from reduced BDNF expression. That BDNF rescues LTP 
      in HD knock-in mice suggests the possibility of treating cognitive deficits in 
      asymptomatic HD gene carriers by upregulating production of the neurotrophin.
FAU - Lynch, Gary
AU  - Lynch G
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine, 
      California 92617-4291, USA.
FAU - Kramar, Eniko A
AU  - Kramar EA
FAU - Rex, Christopher S
AU  - Rex CS
FAU - Jia, Yousheng
AU  - Jia Y
FAU - Chappas, Danielle
AU  - Chappas D
FAU - Gall, Christine M
AU  - Gall CM
FAU - Simmons, Danielle A
AU  - Simmons DA
LA  - eng
GR  - 5T32 AG00096/AG/NIA NIH HHS/United States
GR  - P01 NS045260/NS/NINDS NIH HHS/United States
GR  - T32 AG000096/AG/NIA NIH HHS/United States
GR  - NS051823/NS/NINDS NIH HHS/United States
GR  - NS045260/NS/NINDS NIH HHS/United States
GR  - R01 NS051823/NS/NINDS 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  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dendritic Spines/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Hippocampus/physiopathology
MH  - Huntington Disease/*genetics
MH  - Long-Term Potentiation/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuronal Plasticity/*genetics
MH  - Synapses/metabolism
MH  - Theta Rhythm
PMC - PMC6672319
EDAT- 2007/04/20 09:00
MHDA- 2007/05/08 09:00
PMCR- 2007/10/18
CRDT- 2007/04/20 09:00
PHST- 2007/04/20 09:00 [pubmed]
PHST- 2007/05/08 09:00 [medline]
PHST- 2007/04/20 09:00 [entrez]
PHST- 2007/10/18 00:00 [pmc-release]
AID - 27/16/4424 [pii]
AID - 3208524 [pii]
AID - 10.1523/JNEUROSCI.5113-06.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Apr 18;27(16):4424-34. doi: 10.1523/JNEUROSCI.5113-06.2007.