Quetiapine and repetitive transcranial magnetic stimulation ameliorate
depression-like behaviors and up-regulate the proliferation of
hippocampal-derived neural stem cells in a rat model of depression: The
involvement of the BDNF/ERK signal pathway
Yi-huan Chen
a,1
, Rui-guo Zhang
a,1
,FenXue
a,1
, Hua-ning Wang
a
, Yun-chun Chen
a
, Guang-tao Hu
b
,YePeng
c
,
Zheng-wu Peng
a,
⁎, Qing-rong Tan
a,
⁎
a
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
b
Mental Health Center, 324 Hospital of PLA, Chongqing 400041, China
c
Air Force General Hospital of PLA, Beijing, China
abstractarticle info
Article history:
Received 25 May 2015
Received in revised form 7 July 2015
Accepted 9 July 2015
Available online 12 July 2015
Keywords: Quetiapine rTMS CUS
NSCs
BDNF/ERK
Quetiapine (QUE) and repetitive transcranial magnetic stimulation (rTMS) have been considered to be possible
monotherapies for depression or adjunctive therapies for the treatment of the resistant depression, but the un-
derlying mechanisms remain unclear. The present study aimed to assess the effects of combined QUE and
rTMS treatment on depressive-like behaviors, hippocampal proliferation, and thein vivoandin vitroexpressions
of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) and brain-derived neurotrophic factor
(BDNF) in male Sprague–Dawley rats. The administration of QUE and rTMS was determined not only to reverse
the depressive-like behaviors of rats exposed to chronic unpredictable stress (CUS) but also to restore the protein
expressions of pERK1/2 and BDNF and cell proliferation in the hippocampus. Additionally, QUE and rTMS pro-
moted the proliferation and increased the expression of pERK1/2 and BDNF in hippocampal-derived neural
stem cells (NSCs), and these effects were abolished by U0126. Taken together, these results suggest that the
antidepressive-like effects of QUE and rTMS might be related to the activation of the BDNF/ERK signa
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