PMID- 25849905
OWN - NLM
STAT- MEDLINE
DCOM- 20160331
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of 
      Alzheimer's disease induced by abeta1-42.
PG  - e0122415
LID - 10.1371/journal.pone.0122415 [doi]
LID - e0122415
AB  - An emerging body of data suggests that the early onset of Alzheimer's disease 
      (AD) is associated with decreased brain-derived neurotrophic factor (BDNF). 
      Because BDNF plays a critical role in the regulation of high-frequency synaptic 
      transmission and long-term potentiation in the hippocampus, the up-regulation of 
      BDNF may rescue cognitive impairments and learning deficits in AD. In the present 
      study, we investigated the effects of hippocampal BDNF in a rat model of AD 
      produced by a ventricle injection of amyloid-beta1-42 (Abeta1-42). We found that a 
      ventricle injection of Abeta1-42 caused learning deficits in rats subjected to the 
      Morris water maze and decreased BDNF expression in the hippocampus. Chronic 
      intra-hippocampal BDNF administration rescued learning deficits in the water 
      maze, whereas infusions of NGF and NT-3 did not influence the behavioral 
      performance of rats injected with Abeta1-42. Furthermore, the BDNF-related 
      improvement in learning was ERK-dependent because the inhibition of ERK, but not 
      JNK or p38, blocked the effects of BDNF on cognitive improvement in rats injected 
      with Abeta1-42. Together, our data suggest that the up-regulation of BDNF in the 
      hippocampus via activation of the ERK signaling pathway can ameliorate 
      Abeta1-42-induced learning deficits, thus identifying a novel pathway through which 
      BDNF protects against AD-related cognitive impairments. The results of this 
      research may shed light on a feasible therapeutic approach to control the 
      progression of AD.
FAU - Zhang, Lu
AU  - Zhang L
AD  - Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, China; 
      Department of Neurology, First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Fang, Yu
AU  - Fang Y
AD  - Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, China; 
      Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou 
      University Zhengzhou, Henan, China.
FAU - Lian, Yajun
AU  - Lian Y
AD  - Department of Neurology, First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Chen, Yuan
AU  - Chen Y
AD  - Department of Neurology, First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Wu, Tianwen
AU  - Wu T
AD  - Department of Neurology, First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Zheng, Yake
AU  - Zheng Y
AD  - Department of Neurology, First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Zong, Huili
AU  - Zong H
AD  - Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou 
      University Zhengzhou, Henan, China.
FAU - Sun, Limin
AU  - Sun L
AD  - Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou 
      University Zhengzhou, Henan, China.
FAU - Zhang, Ruifang
AU  - Zhang R
AD  - Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou 
      University Zhengzhou, Henan, China.
FAU - Wang, Zhenhua
AU  - Wang Z
AD  - Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou 
      University Zhengzhou, Henan, China.
FAU - Xu, Yuming
AU  - Xu Y
AD  - Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, China; 
      Department of Neurology, First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150407
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Alzheimer Disease/chemically induced/*drug therapy/enzymology/*physiopathology
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/administration & 
      dosage/metabolism/*pharmacology/therapeutic use
MH  - Cognition/drug effects
MH  - Disease Models, Animal
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Hippocampus/drug effects/metabolism/physiopathology
MH  - Humans
MH  - Injections
MH  - Learning/*drug effects
MH  - Male
MH  - Memory/drug effects
MH  - Peptide Fragments/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spatial Learning/drug effects
MH  - Up-Regulation/drug effects
PMC - PMC4388634
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/08 06:00
MHDA- 2016/04/01 06:00
PMCR- 2015/04/07
CRDT- 2015/04/08 06:00
PHST- 2014/12/04 00:00 [received]
PHST- 2015/02/20 00:00 [accepted]
PHST- 2015/04/08 06:00 [entrez]
PHST- 2015/04/08 06:00 [pubmed]
PHST- 2016/04/01 06:00 [medline]
PHST- 2015/04/07 00:00 [pmc-release]
AID - PONE-D-14-53121 [pii]
AID - 10.1371/journal.pone.0122415 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 7;10(4):e0122415. doi: 10.1371/journal.pone.0122415. 
      eCollection 2015.