Acute Exposure to Pacific Ciguatoxin Reduces Electroencephalogram Activity and Disrupts Neurotransmitter Metabolic Pathways in Motor Cortex.
Ciguatera fish poisoning (CFP) is a common human food poisoning caused by consumption of ciguatoxin (CTX)-contaminated fish affecting over 50,000 people worldwide each year. CTXs are classified depending on their origin from the Pacific (P-CTXs), Indian Ocean (I-CTXs), and Caribbean (C-CTXs). P-CTX-1 is the most toxic CTX known and the major source of CFP causing an array of neurological symptoms. Neurological symptoms in some CFP patients last for several months or years; however, the underlying electrophysiological properties of acute exposure to CTXs remain unknown. Here, we used CTX purified from ciguatera fish sourced in the Pacific Ocean (P-CTX-1). Delta and theta electroencephalography (EEG) activity was reduced remarkably in 2 h and returned to normal in 6 h after a single exposure. However, second exposure to P-CTX-1 induced not only a further reduction in EEG activities but also a 2-week delay in returning to baseline EEG values. Ciguatoxicity was detected in the brain hours after the first and second exposure by mouse neuroblastoma assay. The spontaneous firing rate of single motor cortex neuron was reduced significantly measured by single-unit recording with high spatial resolution. Expression profile study of neurotransmitters using targeted profiling approach based on liquid chromatography-tandem mass spectrometry revealed an imbalance between excitatory and inhibitory neurotransmitters in the motor cortex. Our study provides a possible link between the brain oscillations and neurotransmitter release after acute exposure to P-CTX-1. Identification of EEG signatures and major metabolic pathways affected by P-CTX-1 provides new insight into potential biomarker development and therapeutic interventions.
Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.
Gajendra
G
Kumar
Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.
Ngan Pan Bennett
NPB
Au
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.
Elva Ngai Yu
ENY
Lei
State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, 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.
Yim Ling
YL
Mak
Department of Electronic Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.
Leanne Lai Hang
LLH
Chan
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.
Michael Hon Wah
MHW
Lam
Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.|State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, 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.
Leo Lai
LL
Chan
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.|State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, 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.
Paul Kwan Sing
PKS
Lam
Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong. eddiema@cityu.edu.hk.|State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong. eddiema@cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong. eddiema@cityu.edu.hk.
Chi Him Eddie
CHE
Ma
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D036841:Ciguatera Poisoning / Q000378:metabolism; D002922:Ciguatoxins / Q000633:toxicity*; D004569:Electroencephalography / Q000187:drug effects*; D005399:Fishes; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism*
D018377:Neurotransmitter Agents; D002922:Ciguatoxins
Ciguatera fish poisoning; Delta and theta power; Electroencephalography; Metabolomics; Neurotransmitters; Pacific ciguatoxin-1