Abstract | BACKGROUND: METHODS: The expression level of PICK1 in dorsal root ganglion (DRG) of rats was changed by vector plasmid, and the effect of PICK1 on paclitaxel (PTL)-induced neuralgia of rats was observed in collaboration with FSC231 treatment. The possible molecular mechanisms were explored by quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot and co-immunoprecipitation (Co-IP) techniques. RESULTS: PTL treatment can significantly reduce mechanical withdrawal threshold (MWT), shorten thermal withdrawal latency (TWL), promote DRG inflammation and release of substance P (SP), stimulate PICK1 expression, decrease α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor 2 (AMPAR, GluA2) level and increase glycogen synthase kinase-3β (GSK-3β) and extracellular regulated protein kinases1/2 (ERK1/2) phosphorylation in rats, while FSC231 treatment can alleviate the above effects induced by PTL. Overexpression of PICK1 can counteract reduced PICK1 level, increased GluA2 level and decreased GSK-3β and ERK1/2 phosphorylation levels caused by FSC231 treatment. The results of Co-IP confirmed the interactions between PICK1 and GluA2. Both FSC231 treatment and silent PICK1 improved PTL-induced MWT reduction, TWL shortening, inflammation, SP release and related gene expression changes, with cumulative effect. CONCLUSION:
FSC231 activates GSK-3β/ERK1/2 by inhibiting the interaction between PICK1 and GluA2 and alleviates PTL-induced DRG neuralgia in rats.
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Authors | Xi Zhang, Jiagao Wang, Ran Ran, Yuchuan Peng, Yun Xiao |
Journal | Brain and behavior
(Brain Behav)
Vol. 11
Issue 11
Pg. e2380
(11 2021)
ISSN: 2162-3279 [Electronic] United States |
PMID | 34582111
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC. |
Chemical References |
- Carbamates
- Cinnamates
- FSC 231
- Glycogen Synthase Kinase 3 beta
- Paclitaxel
|
Topics |
- Animals
- Carbamates
- Cinnamates
- Glycogen Synthase Kinase 3 beta
- Neuralgia
(chemically induced, drug therapy)
- Paclitaxel
(toxicity)
- Rats
|