PMID- 25172625
OWN - NLM
STAT- MEDLINE
DCOM- 20150806
LR  - 20220310
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 58
DP  - 2014 Oct
TI  - Repetitive transcranial magnetic stimulation (rTMS) influences spatial cognition 
      and modulates hippocampal structural synaptic plasticity in aging mice.
PG  - 256-68
LID - S0531-5565(14)00247-2 [pii]
LID - 10.1016/j.exger.2014.08.011 [doi]
AB  - Normal aging is characteristic with the gradual decline in cognitive function 
      associated with the progressive reduction of structural and functional plasticity 
      in the hippocampus. Repetitive transcranial magnetic stimulation (rTMS) has 
      developed into a novel neurological and psychiatric tool that can be used to 
      investigate the neurobiology of cognitive function. Recent studies have 
      demonstrated that low-frequency rTMS (</=1Hz) affects synaptic plasticity in rats 
      with vascular dementia (VaD), and it ameliorates the spatial cognitive ability in 
      mice with Abeta1-42-mediated memory deficits, but there are little concerns about 
      the effects of rTMS on normal aging related cognition and synaptic plasticity 
      changes. Thus, the current study investigated the effects of rTMS on spatial 
      memory behavior, neuron and synapse morphology in the hippocampus, and synaptic 
      protein markers and brain-derived neurotrophic factor (BDNF)/tropomyosin-related 
      kinase B (TrkB) in normal aging mice, to illustrate the mechanisms of rTMS in 
      regulating cognitive capacity. Relative to adult animals, aging caused 
      hippocampal-dependent cognitive impairment, simultaneously inhibited the 
      activation of the BDNF-TrkB signaling pathway, reduced the transcription and 
      expression of synaptic protein markers: synaptophysin (SYN), growth associated 
      protein 43 (GAP43) and post-synaptic density protein 95 (PSD95), as well as 
      decreased synapse density and PSD (post-synaptic density) thickness. 
      Interestingly, rTMS with low intensity (110% average resting motor threshold 
      intensity, 1Hz, LIMS) triggered the activation of BDNF and TrkB, upregulated the 
      level of synaptic protein markers, and increased synapse density and thickened 
      PSD, and further reversed the spatial cognition dysfunction in aging mice. 
      Conversely, high-intensity magnetic stimulation (150% average resting motor 
      threshold intensity, 1Hz, HIMS) appeared to be detrimental, inducing thinning of 
      PSDs, disordered synaptic structure, and a large number of lipofuscin 
      accumulations, as well as reducing the number of synapses and downregulating 
      BDNF-TrkB and synaptic proteins. Ultimately, HIMS further impaired the capacity 
      for learning and memory. In conclusion, we infer that aging-induced cognitive 
      deficits are closely associated with hippocampal structural synaptic plasticity, 
      and low-frequency magnetic stimulation plays an important role in regulating 
      cognitive behavior via changing structural synaptic plasticity, and BDNF 
      signaling might participate in this event.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Ma, Jun
AU  - Ma J
AD  - Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, 
      Hebei, PR China; Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, 
      Shijiazhuang 050031, Hebei, PR China.
FAU - Zhang, Zhanchi
AU  - Zhang Z
AD  - Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, 
      Hebei, PR China.
FAU - Kang, Lin
AU  - Kang L
AD  - Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, 
      Hebei, PR China.
FAU - Geng, Dandan
AU  - Geng D
AD  - Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, 
      Hebei, PR China.
FAU - Wang, Yanyong
AU  - Wang Y
AD  - Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, Shijiazhuang 
      050031, Hebei, PR China; First Hospital of Hebei Medical University, Shijiazhuang 
      050031, Hebei, PR China.
FAU - Wang, Mingwei
AU  - Wang M
AD  - Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, Shijiazhuang 
      050031, Hebei, PR China; First Hospital of Hebei Medical University, Shijiazhuang 
      050031, Hebei, PR China.
FAU - Cui, Huixian
AU  - Cui H
AD  - Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, 
      Hebei, PR China; Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, 
      Shijiazhuang 050031, Hebei, PR China. Electronic address: cuihuixianky@yahoo.com.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140827
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (GAP-43 Protein)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Synaptophysin)
RN  - 0 (Syp protein, mouse)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.4.8 (Guanylate Kinases)
SB  - IM
MH  - Age Factors
MH  - Aging/genetics/metabolism/pathology/*psychology
MH  - Animals
MH  - *Behavior, Animal
MH  - Biomarkers/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - *Cognition
MH  - Disks Large Homolog 4 Protein
MH  - GAP-43 Protein/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Guanylate Kinases/genetics/metabolism
MH  - Hippocampus/metabolism/*physiopathology/ultrastructure
MH  - Learning
MH  - Male
MH  - Membrane Proteins/genetics/metabolism
MH  - Memory
MH  - Mice
MH  - *Neuronal Plasticity
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkB/genetics/metabolism
MH  - *Space Perception
MH  - *Synaptic Transmission
MH  - Synaptophysin/genetics/metabolism
MH  - Time Factors
MH  - *Transcranial Magnetic Stimulation
OTO - NOTNLM
OT  - Aging
OT  - Cognition
OT  - Hippocampus
OT  - Repetitive transcranial magnetic stimulation (rTMS)
OT  - Synaptic plasticity
EDAT- 2014/08/31 06:00
MHDA- 2015/08/08 06:00
CRDT- 2014/08/31 06:00
PHST- 2014/03/22 00:00 [received]
PHST- 2014/07/27 00:00 [revised]
PHST- 2014/08/26 00:00 [accepted]
PHST- 2014/08/31 06:00 [entrez]
PHST- 2014/08/31 06:00 [pubmed]
PHST- 2015/08/08 06:00 [medline]
AID - S0531-5565(14)00247-2 [pii]
AID - 10.1016/j.exger.2014.08.011 [doi]
PST - ppublish
SO  - Exp Gerontol. 2014 Oct;58:256-68. doi: 10.1016/j.exger.2014.08.011. Epub 2014 Aug 
      27.