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The direction of synaptic plasticity mediated by C-fibers in spinal dorsal horn is decided by Src-family kinases in microglia: the role of tumor necrosis factor-alpha.
Brain Behav Immun. 2010 Aug; 24(6):874-80.BB

Abstract

Previous studies have shown that Src-family kinases (SFKs) are selectively activated in spinal microglia following peripheral nerve injury and the activated SFKs play a key role for the development of neuropathic pain. To investigate the underlying mechanism, in the present study the effect of SFKs on long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn, which is believed as central mechanism of neuropathic pain, was investigated in adult rats. Electrophysiological data revealed that pretreatment with either microglia inhibitor (minocycline, 200 microM) or SFKs inhibitors (PP2, 100 microM and SU6656, 200 microM) reversed the effect of high frequency stimulation (HFS), that is, HFS, which induces long-term potentiation (LTP) normally, induced long-term depression (LTD) after inhibition of either microglia or SFKs. Western blotting analysis showed that the level of phosphorylated SFKs (p-SFKs) in ipsilateral spinal dorsal horn was transiently increased after LTP induced by HFS, starting at 15 min and returning to control level at 60 min after HFS. Double-labeled immunofluorescence staining demonstrated that p-SFKs were highly restricted to microglia. Furthermore, we found that the inhibitory effects of minocycline or SU6656 on spinal LTP were reversed by spinal application of rat recombinant tumor necrosis factor-alpha (TNF-alpha 0.5 ng/ml, 200 microl). HFS failed to induce LTP of C-fiber evoked field potentials in TNF receptor-1 knockout mice and in rats pretreated with TNF-alpha neutralization antibody (0.6 microg/ml, 200 microl). The results suggested that in spinal dorsal horn activation of SFKs in microglia might control the direction of plastic changes at C-fiber synapses and TNF-alpha might be involved in the process.

Authors+Show Affiliations

Pain Research Center, Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20116424

Citation

Zhong, Yi, et al. "The Direction of Synaptic Plasticity Mediated By C-fibers in Spinal Dorsal Horn Is Decided By Src-family Kinases in Microglia: the Role of Tumor Necrosis Factor-alpha." Brain, Behavior, and Immunity, vol. 24, no. 6, 2010, pp. 874-80.
Zhong Y, Zhou LJ, Ren WJ, et al. The direction of synaptic plasticity mediated by C-fibers in spinal dorsal horn is decided by Src-family kinases in microglia: the role of tumor necrosis factor-alpha. Brain Behav Immun. 2010;24(6):874-80.
Zhong, Y., Zhou, L. J., Ren, W. J., Xin, W. J., Li, Y. Y., Zhang, T., & Liu, X. G. (2010). The direction of synaptic plasticity mediated by C-fibers in spinal dorsal horn is decided by Src-family kinases in microglia: the role of tumor necrosis factor-alpha. Brain, Behavior, and Immunity, 24(6), 874-80. https://doi.org/10.1016/j.bbi.2010.01.007
Zhong Y, et al. The Direction of Synaptic Plasticity Mediated By C-fibers in Spinal Dorsal Horn Is Decided By Src-family Kinases in Microglia: the Role of Tumor Necrosis Factor-alpha. Brain Behav Immun. 2010;24(6):874-80. PubMed PMID: 20116424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The direction of synaptic plasticity mediated by C-fibers in spinal dorsal horn is decided by Src-family kinases in microglia: the role of tumor necrosis factor-alpha. AU - Zhong,Yi, AU - Zhou,Li-Jun, AU - Ren,Wen-Jie, AU - Xin,Wen-Jun, AU - Li,Yong-Yong, AU - Zhang,Tong, AU - Liu,Xian-Guo, Y1 - 2010/01/29/ PY - 2009/10/06/received PY - 2010/01/16/revised PY - 2010/01/19/accepted PY - 2010/2/2/entrez PY - 2010/2/2/pubmed PY - 2010/10/12/medline SP - 874 EP - 80 JF - Brain, behavior, and immunity JO - Brain Behav. Immun. VL - 24 IS - 6 N2 - Previous studies have shown that Src-family kinases (SFKs) are selectively activated in spinal microglia following peripheral nerve injury and the activated SFKs play a key role for the development of neuropathic pain. To investigate the underlying mechanism, in the present study the effect of SFKs on long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn, which is believed as central mechanism of neuropathic pain, was investigated in adult rats. Electrophysiological data revealed that pretreatment with either microglia inhibitor (minocycline, 200 microM) or SFKs inhibitors (PP2, 100 microM and SU6656, 200 microM) reversed the effect of high frequency stimulation (HFS), that is, HFS, which induces long-term potentiation (LTP) normally, induced long-term depression (LTD) after inhibition of either microglia or SFKs. Western blotting analysis showed that the level of phosphorylated SFKs (p-SFKs) in ipsilateral spinal dorsal horn was transiently increased after LTP induced by HFS, starting at 15 min and returning to control level at 60 min after HFS. Double-labeled immunofluorescence staining demonstrated that p-SFKs were highly restricted to microglia. Furthermore, we found that the inhibitory effects of minocycline or SU6656 on spinal LTP were reversed by spinal application of rat recombinant tumor necrosis factor-alpha (TNF-alpha 0.5 ng/ml, 200 microl). HFS failed to induce LTP of C-fiber evoked field potentials in TNF receptor-1 knockout mice and in rats pretreated with TNF-alpha neutralization antibody (0.6 microg/ml, 200 microl). The results suggested that in spinal dorsal horn activation of SFKs in microglia might control the direction of plastic changes at C-fiber synapses and TNF-alpha might be involved in the process. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/20116424/The_direction_of_synaptic_plasticity_mediated_by_C_fibers_in_spinal_dorsal_horn_is_decided_by_Src_family_kinases_in_microglia:_the_role_of_tumor_necrosis_factor_alpha_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(10)00008-5 DB - PRIME DP - Unbound Medicine ER -