Molecular Neurobiology

, Volume 55, Issue 8, pp 6769–6787 | Cite as

Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit

  • Pallavi Asthana
  • Ni Zhang
  • Gajendra Kumar
  • Virendra Bhagawan Chine
  • Kunal Kumar Singh
  • Yim Ling Mak
  • Leo Lai Chan
  • Paul Kwan Sing Lam
  • Chi Him Eddie Ma


Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1. We detected irreversible motor strength deficits accompanied by reduced EMG activity, demyelination, and slowing of motor nerve conduction, whereas control unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally, to uncover the mechanism underlying CFP, we detected reduction of spontaneous firing rate of motor cortical neurons even 6 months after exposure and increased number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Increased numbers of motor cortical neuron apoptosis were detected by dUTP-digoxigenin nick end labeling assay along with activation of caspase 3. Taken together, our study demonstrates that persistence of P-CTX-1 in the nervous system induces irreversible motor deficit that correlates well with excitotoxicity and neurodegeneration detected in the motor cortical neurons.


Ciguatera fish poisoning Pacific ciguatoxin Excitotoxicity Neurodegeneration Apoptosis 



This work is supported in part by The Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong Special Administrative Region Government (Ref. No: 01122016 and 12134101), GRF grants from the Research Grant Council of the Hong Kong Special Administrative Region Government (CityU 11100015 and CityU 160813), SRG (7004587) and ARG (9667149) grants from the City University of Hong Kong award to Chi Ma, and the Collaborative Research Fund, the Research Grant Council of Hong Kong (C1012-15G) award to Paul Lam.

Authors’ Contributions

PA conducted in vivo electrophysiological study, NMJ and MBP quantification, performed sciatic nerve surgery and tissue harvest. NZ carried out the neurobehavioral assessments and data analysis with PA. GK performed single cell neuronal recording and GFAP staining. VBC and KKS performed experiments to confirm cell death. YLM performed P-CTX-1 extraction and tissue distribution analysis with expertise and resources provided by LLC and PKSL CHEM conceived the project and designed the study. PA, GK, and CHEM wrote the manuscript with inputs from all authors. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2018_875_MOESM1_ESM.pdf (701 kb)
ESM 1 (PDF 700 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Pallavi Asthana
    • 1
  • Ni Zhang
    • 1
  • Gajendra Kumar
    • 1
  • Virendra Bhagawan Chine
    • 1
  • Kunal Kumar Singh
    • 1
  • Yim Ling Mak
    • 2
    • 3
  • Leo Lai Chan
    • 1
    • 2
    • 3
  • Paul Kwan Sing Lam
    • 2
    • 3
    • 4
  • Chi Him Eddie Ma
    • 1
    • 2
    • 5
  1. 1.Department of Biomedical SciencesCity University of Hong KongHong KongHong Kong
  2. 2.State Key Laboratory in Marine PollutionCity University of Hong KongHong KongHong Kong
  3. 3.Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human HealthCity University of Hong Kong Shenzhen Research InstituteShenzhenChina
  4. 4.Department of Biology and ChemistryCity University of Hong KongHong KongHong Kong
  5. 5.Centre for Biosystems, Neuroscience, and NanotechnologyCity University of Hong KongHong KongHong Kong

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