title: CPEB3 Deficiency Elevates TRPV1 Expression in Dorsal Root Ganglia Neurons to Potentiate Thermosensation.
abstract: Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that downregulates translation of multiple plasticity-related proteins (PRPs) at the glutamatergic synapses. Activity-induced synthesis of PRPs maintains long-lasting synaptic changes that are critical for memory consolidation and chronic pain manifestation. CPEB3-knockout (KO) mice show aberrant hippocampus-related plasticity and memory, so we investigated whether CPEB3 might have a role in nociception-associated plasticity. CPEB3 is widely expressed in the brain and peripheral afferent sensory neurons. CPEB3-KO mice with normal mechanosensation showed hypersensitivity to noxious heat. In the complete Freund's adjuvant (CFA)-induced inflammatory pain model, CPEB3-KO animals showed normal thermal hyperalgesia and transiently enhanced mechanical hyperalgesia. Translation of transient receptor potential vanilloid 1 (TRPV1) RNA was suppressed by CPEB3 in dorsal root ganglia (DRG), whereas CFA-induced inflammation reversed this inhibition. Moreover, CPEB3/TRPV1 double-KO mice behaved like TRPV1-KO mice, with severely impaired thermosensation and thermal hyperalgesia. An enhanced thermal response was recapitulated in non-inflamed but not inflamed conditional-KO mice, with cpeb3 gene ablated mostly but not completely, in small-diameter nociceptive DRG neurons. CPEB3-regulated translation of TRPV1 RNA may play a role in fine-tuning thermal sensitivity of nociceptors.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Sitt Wai
authors.initials: SW
authors.lastname: Fong
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsiu-Chen
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Meng-Fang
authors.initials: MF
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
mesh_terms: D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology*; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics*; D013697:Thermosensing / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C477603:Cpeb3 protein, mouse; D016601:RNA-Binding Proteins; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012313:RNA