l-Serine Reduces Spinal Cord Pathology in a Vervet Model of Preclinical ALS/MND

David A. Davis, Paul Alan Cox, Sandra Anne Banack, Patricia D. Lecusay, Susanna P. Garamszegi, Matthew J. Hagan, James T. Powell, James S. Metcalf, Roberta M. Palmour, Amy Beierschmitt, Walter G. Bradley, Deborah C. Mash

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The early neuropathological features of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are protein aggregates in motor neurons and microglial activation. Similar pathology characterizes Guamanian ALS/Parkinsonism dementia complex, which may be triggered by the cyanotoxin β-N-methylamino-l-alanine (BMAA). We report here the occurrence of ALS/MND-type pathological changes in vervets (Chlorocebus sabaeus; n = 8) fed oral doses of a dry powder of BMAA HCl salt (210 mg/kg/day) for 140 days. Spinal cords and brains from toxin-exposed vervets were compared to controls fed rice flour (210 mg/kg/day) and to vervets coadministered equal amounts of BMAA and l-serine (210 mg/kg/day). Immunohistochemistry and quantitative image analysis were used to examine markers of ALS/MND and glial activation. UHPLC-MS/MS was used to confirm BMAA exposures in dosed vervets. Motor neuron degeneration was demonstrated in BMAA-dosed vervets by TDP-43+ proteinopathy in anterior horn cells, by reactive astrogliosis, by activated microglia, and by damage to myelinated axons in the lateral corticospinal tracts. Vervets dosed with BMAA + l-serine displayed reduced neuropathological changes. This study demonstrates that chronic dietary exposure to BMAA causes ALS/MND-type pathological changes in the vervet and coadministration of l-serine reduces the amount of reactive gliosis and the number of protein inclusions in motor neurons.

Original languageEnglish (US)
Pages (from-to)393-406
Number of pages14
JournalJournal of neuropathology and experimental neurology
Volume79
Issue number4
DOIs
StatePublished - Apr 1 2020

Keywords

  • ALS/MND
  • BMAA
  • Cyanobacteria
  • Guam ALS/PDC
  • Motor neurons
  • Neurofibrillary tangles
  • TDP-43

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Davis, D. A., Cox, P. A., Banack, S. A., Lecusay, P. D., Garamszegi, S. P., Hagan, M. J., Powell, J. T., Metcalf, J. S., Palmour, R. M., Beierschmitt, A., Bradley, W. G., & Mash, D. C. (2020). l-Serine Reduces Spinal Cord Pathology in a Vervet Model of Preclinical ALS/MND. Journal of neuropathology and experimental neurology, 79(4), 393-406. https://doi.org/10.1093/jnen/nlaa002