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

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 definit...

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Published in:Neuromolecular medicine 2002-01, Vol.1 (3), p.207-222
Main Authors: Wilson, Jason M B, Khabazian, Iraj, Wong, Margaret C, Seyedalikhani, Arash, Bains, Jaswinder S, Pasqualotto, Bryce A, Williams, David E, Andersen, Raymond J, Simpson, Rebecca J, Smith, Richard, Craig, Ulla-Kate, Kurland, Leonard T, Shaw, Christopher A
Format: Article
Language:English
Subjects:
Amyotrophic Lateral Sclerosis - chemically induced
Amyotrophic Lateral Sclerosis - metabolism
Amyotrophic Lateral Sclerosis - physiopathology
Animals
Behavior
Behavior, Animal - drug effects
Behavior, Animal - physiology
Central Nervous System - drug effects
Central Nervous System - pathology
Central Nervous System - physiopathology
Chromatography
Cycas - chemistry
Dementia
Lameness, Animal - chemically induced
Lameness, Animal - pathology
Lameness, Animal - physiopathology
Male
Mass spectrometry
Memory Disorders - chemically induced
Memory Disorders - pathology
Memory Disorders - physiopathology
Mice
Mice, Inbred Strains
Neurodegeneration
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Neurotoxins - toxicity
Plant Extracts - toxicity
Rats
Reaction Time - drug effects
Reaction Time - physiology
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Summary: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 beta-sitosterol beta-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.
ISSN:1535-1084
1559-1174
1535-1084
DOI:10.1385/nmm:1:3:207