首页|CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain

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Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms.The circRNAs are mainly enriched in the central nervous system.However,their function in various physiological and pathological conditions have yet to be determined.Here,we identified circFhit,an exon-intron circRNA expressed in GABAergic neurons,which reduced the inhibitory synap-tic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain.Moreover,we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+neurons by promoting the expression of its parental gene Fhit in cis.Mechanistically,circFhit was directly bound to the intronic region of Fhit,and formed a circFhit/HNRNPK complex to promote Pol Ⅱphosphorylation and H2B monoubiquitination by recruit-ing CDK9 and RNF40 to the Fhit intron.In summary,we revealed that the exon-intron circFhit contributes to GABAe-rgic neuron-mediated NK1R+neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Chronic painNeuropathic painCircRNAInhibitory transmissionEpigenetic regulation

Ting Xu、Zhen-Yu Li、Meng Liu、Su-Bo Zhang、Huan-Huan Ding、Jia-Yan Wu、Su-Yan Lin、Jun Liu、Jia-You Wei、Xue-Qin Zhang、Wen-Jun Xin

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Neuroscience Program of Zhongshan School of Medicine and the Fifth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China

Guangdong Province Key Laboratory of Brain Function and Disease,Sun Yat-sen University,Guangzhou 510120,China

Department of Anesthesia and Pain Medicine,Guangzhou First People's Hospital,Guangzhou 510000,China

Department of Physiology,Xuzhou Medical University,Xuzhou 221004,China

Department of Neurology,The Second Affiliated Hospital,Guangzhou Medical University,Guangzhou 510000,China

Guangdong Provincial Engineering Research Center of Molecular Imaging,Guangdong Provincial Key Laboratory of Biomedical Imaging,and Department of Interventional Medicine,The Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai 519000,China

The Affiliated Brain Hospital(Guangzhou Huiai Hospital)and School of Health Management,Guangzhou Medical University,Guangzhou 510182,China

Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou 510000,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaScience and Technology Program of GuangdongNatural Science Foundation of GuangdongNatural Science Foundation of GuangdongNatural Science Foundation of GuangdongGuangzhou Science and Technology Plan ProjectNatural Science Foundation of JiangsuFundamental Research Funds for the Central Universities

3197009368180110381901127821013072018B0303340012019A15150108712019A15150106452022A1515010414201803010006BK2021090419ykpy44

2023

10.1007/s12264-022-01014-5

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(6)
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