AUTHOR=Maruyama Takashi , Tanabe Shogo , Uyeda Akiko , Suzuki Tatsunori , Muramatsu Rieko 

TITLE=Free fatty acids support oligodendrocyte survival in a mouse model of amyotrophic lateral sclerosis

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1081190

DOI=10.3389/fncel.2023.1081190

ISSN=1662-5102

ABSTRACT=<sec><title>Introduction</title><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the white matter degeneration. Although changes in blood lipids are involved in the pathogenesis of neurological diseases, the pathological role of blood lipids in ALS remains unclear.</p></sec><sec><title>Methods and results</title><p>We performed lipidome analysis on the plasma of ALS model mice, mutant superoxide dismutase 1 (SOD1<sup><italic>G</italic>93<italic>A</italic></sup>) mice, and found that the concentration of free fatty acids (FFAs), including oleic acid (OA) and linoleic acid (LA), decreased prior to disease onset. An <italic>in vitro</italic> study revealed that OA and LA directly inhibited glutamate-induced oligodendrocytes cell death via free fatty acid receptor 1 (FFAR1). A cocktail containing OA/LA suppressed oligodendrocyte cell death in the spinal cord of SOD1<sup><italic>G</italic>93<italic>A</italic></sup> mice.</p></sec><sec><title>Discussion</title><p>These results suggested that the reduction of FFAs in the plasma is a pathogenic biomarker for ALS in the early stages, and supplying a deficiency in FFAs is a potential therapeutic approach for ALS by preventing oligodendrocyte cell death.</p></sec>