Open Accessl-Serine Reduces Spinal Cord Pathology in a Vervet Model of Preclinical ALS/MND
Author(s) -
Davis Da,
Paul Alan Cox,
Sandra Anne Banack,
Patricia D Lecusay,
Susanna P. Garamszegi,
Matthew Hagan,
James T. Powell,
James S. Metcalf,
Roberta M. Palmour,
Amy Beierschmitt,
Walter G. Bradley,
Deborah C. Mash
Publication year - 2020
Publication title -
journal of neuropathology and experimental neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.441
H-Index - 164
eISSN - 1554-6578
pISSN - 0022-3069
DOI - 10.1093/jnen/nlaa002
Subject(s) - astrogliosis , amyotrophic lateral sclerosis , gliosis , pathology , spinal cord , neurodegeneration , medicine , pathological , biology , neuroscience , central nervous system , disease
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.