Full Text:   <2204>

Summary:  <1688>

CLC number: R493

On-line Access: 2016-07-06

Received: 2015-12-02

Revision Accepted: 2016-03-31

Crosschecked: 2016-06-23

Cited: 1

Clicked: 3476

Citations:  Bibtex RefMan EndNote GB/T7714


Qing-ping Tang


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.7 P.493-502


STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats

Author(s):  Qing-ping Tang, Qin Shen, Li-xiang Wu, Xiang-ling Feng, Hui Liu, Bei Wu, Xiao-song Huang, Gai-qing Wang, Zhong-hao Li, Zun-jing Liu

Affiliation(s):  Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha 410007, China; more

Corresponding email(s):   liuzunjing@163.com

Key Words:  Motor training, Signal transducer and activator of transcription 3 (STAT3), Brain-derived neurotrophic factor (BDNF), Protein interacting with C kinase 1 (PICK1), Neural plasticity

Share this article to: More |Next Article >>>

Qing-ping Tang, Qin Shen, Li-xiang Wu, Xiang-ling Feng, Hui Liu, Bei Wu, Xiao-song Huang, Gai-qing Wang, Zhong-hao Li, Zun-jing Liu. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats[J]. Journal of Zhejiang University Science B, 2016, 17(7): 493-502.

@article{title="STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats",
author="Qing-ping Tang, Qin Shen, Li-xiang Wu, Xiang-ling Feng, Hui Liu, Bei Wu, Xiao-song Huang, Gai-qing Wang, Zhong-hao Li, Zun-jing Liu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats
%A Qing-ping Tang
%A Qin Shen
%A Li-xiang Wu
%A Xiang-ling Feng
%A Hui Liu
%A Bei Wu
%A Xiao-song Huang
%A Gai-qing Wang
%A Zhong-hao Li
%A Zun-jing Liu
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 7
%P 493-502
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500297

T1 - STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats
A1 - Qing-ping Tang
A1 - Qin Shen
A1 - Li-xiang Wu
A1 - Xiang-ling Feng
A1 - Hui Liu
A1 - Bei Wu
A1 - Xiao-song Huang
A1 - Gai-qing Wang
A1 - Zhong-hao Li
A1 - Zun-jing Liu
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 7
SP - 493
EP - 502
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500297

Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Antoniou, A., Baptista, M., Carney, N., et al., 2014. PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity. EMBO Rep., 15(5):548-556.

[2]Ashwal, S., Tone, B., Tian, H.R., et al., 1998. Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke, 29(5):1037-1046, discussion 1047.

[3]Bliss, T.V., Collingridge, G.L., 1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 361(6407):31-39.

[4]Bouret, S.G., Bates, S.H., Chen, S., et al., 2012. Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits. J. Neurosci., 32(4):1244-1252.

[5]Chang, Y.J., Chen, K.W., Chen, C.J., et al., 2014. SH2B1β interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation. Mol. Cell. Biol., 34(6):1003-1019.

[6]Citri, A., Bhattacharyya, S., Ma, C., et al., 2010. Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression. J. Neurosci., 30(49):16437-16452.

[7]Dominguez, E., Mauborgne, A., Mallet, J., et al., 2010. SOCS3-mediated blockade of JAK/STAT3 signaling pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after peripheral nerve injury. J. Neurosci., 30(16):5754-5766.

[8]Doyle, S., Pyndiah, S., de Gois, S., et al., 2010. Excitation-transcription coupling via calcium/calmodulin-dependent protein kinase/ERK1/2 signaling mediates the coordinate induction of VGLUT2 and Narp triggered by a prolonged increase in glutamatergic synaptic activity. J. Biol. Chem., 285(19):14366-14376.

[9]Dziennis, S., Alkayed, N.J., 2008. Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration. Rev. Neurosci., 19(4-5):341-361.

[10]Gao, J., Wang, W.Y., Mao, Y.W., et al., 2010. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature, 466(7310):1105-1109.

[11]Gómez-Pinilla, F., Ying, Z., Roy, R.R., et al., 2002. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J. Neurophysiol., 88(5):2187-2195.

[12]Gordon, S.L., Leube, R.E., Cousin, M.A., 2011. Synaptophysin is required for synaptobrevin retrieval during synaptic vesicle endocytosis. J. Neurosci., 31(39):14032-14036.

[13]Hu, Z.L., Huang, C., Fu, H., et al., 2010. Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs. Am. J. Physiol. Cell Physiol., 299(6):C1355-C1362.

[14]Huang, J., Du, F.L., Yao, Y., et al., 2015. Numerical magnitude processing in abacus-trained children with superior mathematical ability: an EEG study. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 16(8):661-671.

[15]Jones, T.A., Chu, C.J., Grande, L.A., et al., 1999. Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. J. Neurosci., 19(22):10153-10163.

[16]Kwon, S.E., Chapman, E.R., 2011. Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons. Neuron, 70(5):847-854.

[17]Lei, C., Deng, J., Wang, B., et al., 2011. Reactive oxygen species scavenger inhibits STAT3 activation after transient focal cerebral ischemia-reperfusion injury in rats. Anesth. Analg., 113(1):153-159.

[18]Liang, Y.J., Wu, D.F., Yang, L.Q., et al., 2007. Interaction of the µ-opioid receptor with synaptophysin influences receptor trafficking and signaling. Mol. Pharmacol., 71(1):123-131.

[19]Liu, H., Honmou, O., Harada, K., et al., 2006. Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain, 129(Pt 10):2734-2745.

[20]Liu, R.Y., Snider, W.D., 2001. Different signaling pathways mediate regenerative versus developmental sensory axon growth. J. Neurosci., 21(17):RC164.

[21]MacLellan, C.L., Keough, M.B., Granter-Button, S., et al., 2011. A critical threshold of rehabilitation involving brain-derived neurotrophic factor is required for poststroke recovery. Neurorehabil. Neural. Repair., 25(8):740-748.

[22]Maldonado, M.A., Allred, R.P., Felthauser, E.L., et al., 2008. Motor skill training, but not voluntary exercise, improves skilled reaching after unilateral ischemic lesions of the sensorimotor cortex in rats. Neurorehabil. Neural. Repair., 22(3):250-261.

[23]Mullen, R.J., Buck, C.R., Smith, A.M., 1992. NeuN, a neuronal specific nuclear protein in vertebrates. Development, 116(1):201-211.

[24]Nakai, T., Nagai, T., Tanaka, M., et al., 2014. Girdin phosphorylation is crucial for synaptic plasticity and memory: a potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor. J. Neurosci., 34(45):14995-15008.

[25]Ng, Y.P., Cheung, Z.H., Ip, N.Y., 2006. STAT3 as a downstream mediator of Trk signaling and functions. J. Biol. Chem., 281(23):15636-15644.

[26]Niture, S.K., Jaiswal, A.K., 2012. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J. Biol. Chem., 287(13):9873-9886.

[27]Oatley, J.M., Kaucher, A.V., Avarbock, M.R., et al., 2010. Regulation of mouse spermatogonial stem cell differentiation by STAT3 signaling. Biol. Reprod., 83(3):427-433.

[28]Ploughman, M., Windle, V., MacLellan, C.L., et al., 2009. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke, 40(4):1490-1495.

[29]Quarta, S., Baeumer, B.E., Scherbakov, N., et al., 2014. Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130. J. Neurosci., 34(39):13222-13233.

[30]Schabitz, W.R., Li, F., Irie, K., et al., 1999. Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia. Stroke, 30(2):427-431, discussion 431-432.

[31]Selvaraj, B.T., Frank, N., Bender, F.L., et al., 2012. Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease. J. Cell Biol., 199(3):437-451.

[32]Seo, H.G., Kim, D.Y., Park, H.W., et al., 2010. Early motor balance and coordination training increased synaptophysin in subcortical regions of the ischemic rat brain. J. Korean Med. Sci., 25(11):1638-1645.

[33]Shulga, N., Pastorino, J.G., 2012. GRIM-19-mediated translocation of STAT3 to mitochondria is necessary for TNF-induced necroptosis. J. Cell Sci., 125(Pt 12):2995-3003.

[34]Suzuki, S., Tanaka, K., Nogawa, S., et al., 2001. Phosphorylation of signal transducer and activator of transcription-3 (Stat3) after focal cerebral ischemia in rats. Exp. Neurol., 170(1):63-71.

[35]Tang, Q.P., Yang, Q.D., Wu, Y.H., et al., 2005. Effects of problem-oriented willed-movement therapy on motor abilities for people with poststroke cognitive deficits. Phys. Ther., 85(10):1020-1033.

[36]Tang, Q.P., Yang, Q.D., Hu, Z.Y., et al., 2007. The effects of willed movement therapy on AMPA receptor properties for adult rat following focal cerebral ischemia. Behav. Brain Res., 181(2):254-261.

[37]Tang, Q.P., Tan, L.H., Yang, X.S., et al., 2013. Willed-movement training reduces motor deficits and induces a PICK1-dependent LTD in rats subjected to focal cerebral ischemia. Behav. Brain Res., 256:481-487.

[38]Volk, L., Kim, C.H., Takamiya, K., et al., 2010. Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning. PNAS, 107(50):21784-21789.

[39]Waterhouse, E.G., An, J.J., Orefice, L.L., et al., 2012. BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission. J. Neurosci., 32(41):14318-14330.

[40]Wilhelm, J.C., Xu, M., Cucoranu, D., et al., 2012. Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration. J. Neurosci., 32(14):5002-5009.

[41]Xu, J., Kam, C., Luo, J.H., et al., 2014. PICK1 mediates synaptic recruitment of AMPA receptors at neurexin-induced postsynaptic sites. J. Neurosci., 34(46):15415-15424.

[42]Yadav, A., Kalita, A., Dhillon, S., et al., 2005. JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3. J. Biol. Chem., 280(36):31830-31840.

[43]Yoshimatsu, T., Kawaguchi, D., Oishi, K., et al., 2006. Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex. Development, 133(13):2553-2563.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE