PMID- 28911966
OWN - NLM
STAT- MEDLINE
DCOM- 20180612
LR  - 20180612
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 126
DP  - 2017 Nov
TI  - Fluoxetine administration during adolescence attenuates cognitive and synaptic 
      deficits in adult 3xTgAD mice.
PG  - 200-212
LID - S0028-3908(17)30416-1 [pii]
LID - 10.1016/j.neuropharm.2017.08.037 [doi]
AB  - Fluoxetine (FLX) has broad neurobiological functions and neuroprotective effects; 
      however, the preventive effects of FLX on cognitive impairments in Alzheimer's 
      disease (AD) have not been reported. Here, we studied whether adolescent 
      administration of fluoxetine can prevent memory deficits in AD transgenic mice 
      that harbour PS1(m146v), APP(swe) and TauP(301L) mutations (3 x TgAD). FLX was 
      applied through peritoneal injection to the mice at postnatal day 35 (p35) for 15 
      consecutive days, and the effects of FLX were observed at 6-month. We found that 
      adolescent administration of FLX improved learning and memory abilities in 
      6-month-old 3 x TgAD mice. FLX exposure also increased the sizes of the 
      hippocampal CA1, dentate gyrus (DG) and extensive cortex regions, with increased 
      numbers of neurons and higher dendritic spine density. Meanwhile, the synaptic 
      plasticity of neurons in the hippocampus was remodelled, and the expression 
      levels of synaptic-related proteins were increased along with activation of the 
      cyclic AMP response element-binding (CREB) protein/brain-derived neurotrophic 
      factor (BDNF) signalling pathway. Finally, we found that FLX effectively 
      prevented the increase of beta-amyloid (Abeta) levels. These data suggest that 
      adolescent administration of the antidepressant drug FLX can efficiently preserve 
      cognitive functions and improve pathologies in 3xTg AD mice.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Sun, Dong-Sheng
AU  - Sun DS
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of Ministry of Education of 
      China for Neurological Disorders, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430030, China.
FAU - Gao, Li-Feng
AU  - Gao LF
AD  - National Center for Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic 
      Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and 
      Mathematics, Chinese Academy of Sciences, Wuhan, China.
FAU - Jin, Li
AU  - Jin L
AD  - Department of Pathophysiology, Henan Medical College, Zhengzhou 451191, China; 
      Henan Key Laboratory of Degenerative Brain Disease, Henan Medical College, 
      Zhengzhou 451191, China.
FAU - Wu, Hao
AU  - Wu H
AD  - National Center for Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic 
      Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and 
      Mathematics, Chinese Academy of Sciences, Wuhan, China.
FAU - Wang, Qun
AU  - Wang Q
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of Ministry of Education of 
      China for Neurological Disorders, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430030, China.
FAU - Zhou, You
AU  - Zhou Y
AD  - Department of Neurosurgery, Tianyou Hospital, Wuhan University of Science and 
      Technology, Wuhan, China.
FAU - Fan, Shuhao
AU  - Fan S
AD  - Department of Neurosurgery, Tianyou Hospital, Wuhan University of Science and 
      Technology, Wuhan, China.
FAU - Jiang, Xia
AU  - Jiang X
AD  - Department of Pathology, Hubei University of Chinese Medicine, Wuhan 430030, 
      China.
FAU - Ke, Dan
AU  - Ke D
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of Ministry of Education of 
      China for Neurological Disorders, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430030, China.
FAU - Lei, Hao
AU  - Lei H
AD  - National Center for Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic 
      Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and 
      Mathematics, Chinese Academy of Sciences, Wuhan, China. Electronic address: 
      leihao@wipm.ac.cn.
FAU - Wang, Jian-Zhi
AU  - Wang JZ
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of Ministry of Education of 
      China for Neurological Disorders, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430030, China; Co-Innovation Center of 
      Neuroregeneration, Nantong University, Nantong JS 226001, China. Electronic 
      address: wangjz@mails.tjmu.edu.cn.
FAU - Liu, Gong-Ping
AU  - Liu GP
AD  - Department of Pathophysiology, School of Basic Medicine and the Collaborative 
      Innovation Center for Brain Science, Key Laboratory of Ministry of Education of 
      China for Neurological Disorders, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430030, China; Co-Innovation Center of 
      Neuroregeneration, Nantong University, Nantong JS 226001, China. Electronic 
      address: liugp111@mail.hust.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170911
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Alzheimer Disease/*metabolism/prevention & control/*psychology
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Brain/drug effects/pathology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dendritic Spines/drug effects
MH  - Disease Models, Animal
MH  - Fluoxetine/*administration & dosage
MH  - Learning/drug effects
MH  - Long-Term Potentiation/drug effects
MH  - Male
MH  - Memory/drug effects
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurons/drug effects
MH  - Synapses/*drug effects/metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - BDNF
OT  - Cognitive
OT  - Fluoxetine
OT  - MRI
EDAT- 2017/09/16 06:00
MHDA- 2018/06/13 06:00
CRDT- 2017/09/16 06:00
PHST- 2016/12/15 00:00 [received]
PHST- 2017/08/28 00:00 [revised]
PHST- 2017/08/30 00:00 [accepted]
PHST- 2017/09/16 06:00 [pubmed]
PHST- 2018/06/13 06:00 [medline]
PHST- 2017/09/16 06:00 [entrez]
AID - S0028-3908(17)30416-1 [pii]
AID - 10.1016/j.neuropharm.2017.08.037 [doi]
PST - ppublish
SO  - Neuropharmacology. 2017 Nov;126:200-212. doi: 10.1016/j.neuropharm.2017.08.037. 
      Epub 2017 Sep 11.