PMID- 19264961
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20220321
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 12
DP  - 2009 Mar 24
TI  - Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in 
      Huntington's disease knockin mice.
PG  - 4906-11
LID - 10.1073/pnas.0811228106 [doi]
AB  - Cognitive problems occur in asymptomatic gene carriers of Huntington's disease 
      (HD), and mouse models of the disease exhibit impaired learning and substantial 
      deficits in the cytoskeletal changes that stabilize long-term potentiation (LTP). 
      The latter effects may be related to the decreased production of brain-derived 
      neurotrophic factor (BDNF) associated with the HD mutation. This study asked 
      whether up-regulating endogenous BDNF levels with an ampakine, a positive 
      modulator of AMPA-type glutamate receptors, rescues plasticity and reduces 
      learning problems in HD (CAG140) mice. Twice-daily injections of a short 
      half-life ampakine normalized BDNF levels, activity-driven actin polymerization 
      in dendritic spines, and LTP stabilization in 8-week-old mutants. Comparable 
      results were obtained in 16-week-old HD mice with more severe LTP deficits. 
      Ampakine treatments had no measurable effect on the decreased locomotor activity 
      observed in the mutants but offset their impairments in long-term memory. Given 
      that ampakines are well tolerated in clinical trials and were effective in this 
      study after brief exposures, these results suggest a novel strategy for chronic 
      treatment of the cognitive difficulties that occur in the early stages of HD.
FAU - Simmons, Danielle A
AU  - Simmons DA
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine, CA 
      92617-4291, USA. danielle.a.simmons@gmail.com.
FAU - Rex, Christopher S
AU  - Rex CS
FAU - Palmer, Linda
AU  - Palmer L
FAU - Pandyarajan, Vijay
AU  - Pandyarajan V
FAU - Fedulov, Vadim
AU  - Fedulov V
FAU - Gall, Christine M
AU  - Gall CM
FAU - Lynch, Gary
AU  - Lynch G
LA  - eng
GR  - R01 NS051823/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  - P01 NS045260/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090305
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Actins/metabolism
MH  - Aging/drug effects/pathology
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Gene Knock-In Techniques
MH  - Hippocampus/drug effects/metabolism
MH  - Humans
MH  - Huntington Disease/complications/*physiopathology
MH  - Long-Term Potentiation/drug effects
MH  - Male
MH  - Memory/*drug effects
MH  - Memory Disorders/complications
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Neuronal Plasticity/*drug effects
MH  - Synapses/*drug effects
MH  - Time Factors
MH  - Up-Regulation/*drug effects
PMC - PMC2660722
COIS- Conflict of interest statement: G.L. is a consultant for and has financial 
      interests in Cortex Pharmaceuticals, Inc., which provided the ampakine used in 
      this study.
EDAT- 2009/03/07 09:00
MHDA- 2009/04/09 09:00
PMCR- 2009/09/24
CRDT- 2009/03/07 09:00
PHST- 2009/03/07 09:00 [entrez]
PHST- 2009/03/07 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2009/09/24 00:00 [pmc-release]
AID - 0811228106 [pii]
AID - 7241 [pii]
AID - 10.1073/pnas.0811228106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4906-11. doi: 
      10.1073/pnas.0811228106. Epub 2009 Mar 5.