JOURNAL ARTICLE

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

Yi Zhong, Li-Jun Zhou, Wen-Jie Ren, Wen-Jun Xin, Yong-Yong Li, Tong Zhang, Xian-Guo Liu
Brain, Behavior, and Immunity 2010, 24 (6): 874-80
20116424
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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
20116424
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"