CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain
© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences..
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 synaptic 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 II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Neuroscience bulletin - 39(2023), 6 vom: 13. Juni, Seite 947-961 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Ting [VerfasserIn] |
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| Links: |
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| Themen: |
Chronic pain |
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| Anmerkungen: |
Date Completed 15.06.2023 Date Revised 16.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12264-022-01014-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351487360 |
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| 245 | 1 | 0 | |a 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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| 500 | |a Date Revised 16.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences. | ||
| 520 | |a 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 synaptic 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 II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic pain | |
| 650 | 4 | |a CircRNA | |
| 650 | 4 | |a Epigenetic regulation | |
| 650 | 4 | |a Inhibitory transmission | |
| 650 | 4 | |a Neuropathic pain | |
| 700 | 1 | |a Li, Zhen-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Su-Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Huan-Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jia-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Su-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Jia-You |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xue-Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Wen-Jun |e verfasserin |4 aut | |
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