NeuroMolecular Medicine

, Volume 1, Issue 3, pp 207–221 | Cite as

Behavioral and neurological correlates of ALS-parkinsonism dementia complex in adult mice fed washed cycad flour

  • Jason M. B. Wilson
  • Iraj Khabazian
  • Margaret C. Wong
  • Arash Seyedalikhani
  • Jaswinder S. Bains
  • Bryce A. Pasqualotto
  • David E. Williams
  • Raymond J. Andersen
  • Rebecca J. Simpson
  • Richard Smith
  • Ulla-Kate Craig
  • Leonard T. Kurland
  • Christopher A. Shaw
Original Research

Abstract

Consumption of cycad seed products (Cycas circinalis) is one of the strongest epidemiological links to the Guamian neurological disorder amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), however, the putative toxin which causes neurodegeneration has never been identified definitively. To reexamine this issue, 6–7-mo-old, male CD-1 mice were assessed for motor and cognitive behaviours during and following feeding with pellets made from washed cycad flour. Cycad-fed animals showed early evidence of progressive motor and cognitive dysfunctions. Neurodegeneration measured using TUNEL and caspase-3 labeling was found in neocortex, various hippocampal fields, substantia nigra, olfactory bulb, and spinal cord. In vitro studies using rat neocortex have identified toxic compounds in washed cycad flour that induce depolarizing field potentials and lead to release of lactate dehydrogenase (LDH), both blocked by AP5. High-performance liquid chromatography (HPLC)/mass spectrometry of cycad flour samples failed to show appreciable amounts of other known cycad toxins, cycasin, MAM, or BMAA; only trace amounts of BOAA were present. Isolation procedures employing these techniques identified the most toxic component as β-sitosterol β-d-glucoside (BSSG). The present data suggest that a neurotoxin, or a toxic metabolite, not previously identified in cycad, is able to gain access to central nervous system (CNS) resulting in neurodegeneration of specific neural populations and in motor and cognitive dysfunctions. These data are consistent with a number of major features of ALS-PDC in humans.

Index Entries

ALS-PDC dementia Alzheimer’s disease parkinsonism ALS cycad neurodegeneration neurotoxicity 

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Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Jason M. B. Wilson
    • 1
    • 4
  • Iraj Khabazian
    • 1
  • Margaret C. Wong
    • 1
    • 4
  • Arash Seyedalikhani
    • 1
  • Jaswinder S. Bains
    • 1
  • Bryce A. Pasqualotto
    • 2
  • David E. Williams
    • 3
  • Raymond J. Andersen
    • 3
  • Rebecca J. Simpson
    • 1
  • Richard Smith
    • 5
  • Ulla-Kate Craig
    • 6
  • Leonard T. Kurland
    • 7
  • Christopher A. Shaw
    • 1
    • 2
    • 4
  1. 1.Department of OphthalmologyUniversity of British ColumbiaVancouver
  2. 2.Department of PhysiologyUniversity of British ColumbiaVancouver
  3. 3.Department of ChemistryUniversity of British ColumbiaVancouver
  4. 4.Department of Neuroscience ProgrammeUniversity of British ColumbiaVancouver
  5. 5.Center for Neurological StudyLa Jolla
  6. 6.Bodig and Lytico Research ProjectUniversity of GuamMangilaoGuam
  7. 7.Mayo ClinicRochester

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