title: Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.
abstract: Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Ngan Pan Bennett
authors.initials: NP
authors.lastname: Au
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Gajendra
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Asthana
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Chung
authors.initials: C
authors.lastname: Tin
authors.affiliation: State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Yim Ling
authors.initials: YL
authors.lastname: Mak
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Leo Lai
authors.initials: LL
authors.lastname: Chan
authors.affiliation: State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.|Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Paul Kwan Sing
authors.initials: PK
authors.lastname: Lam
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Tat Chee Avenue, Hong Kong.|State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Chi Him Eddie
authors.initials: CH
authors.lastname: Ma
mesh_terms: D000818:Animals; D019771:Axotomy; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002922:Ciguatoxins / Q000032:analysis / Q000633:toxicity*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D009068:Movement / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D000071446:Neuronal Outgrowth / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000503:physiopathology*; D011042:Poisons / Q000008:administration & dosage / Q000633:toxicity*; D020127:Recovery of Function
chemical_list: D011042:Poisons; D002922:Ciguatoxins