RT Journal Article
SR Electronic
T1 An intestinal sphingolipid promotes neuronal health across generations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.24.501274
DO 10.1101/2022.07.24.501274
A1 Wang, Wenyue
A1 Sherry, Tessa
A1 Cheng, Xinran
A1 Fan, Qi
A1 Cornell, Rebecca
A1 Liu, Jie
A1 Xiao, Zhicheng
A1 Pocock, Roger
YR 2022
UL http://biorxiv.org/content/early/2022/07/24/2022.07.24.501274.abstract
AB Maternal diet and environment can influence the neuronal health of offspring. Here, we report that diet-induced intestinal sphingolipid biosynthesis reduces adult-onset neurodegeneration intergenerationally in Caenorhabditis elegans. Feeding C. elegans with ursolic acid (UA), a natural plant product, provides neuroprotection by enhancing maternal provisioning of sphingosine-1-phosphate (S1P) - a bioactive sphingolipid. S1P promotes neuronal health across generations by upregulating transcription of the acid ceramidase-1 (asah-1) gene in the intestine. Intergenerational intestine-to-oocyte S1P transfer is essential for promoting neuronal health and is dependent on the lipoprotein yolk receptor RME-2 (Receptor-Mediated Endocytosis-2). Spatially regulating sphingolipid biosynthesis is critical, as inappropriate asah-1 neuronal expression causes developmental axon outgrowth defects. Our results reveal that sphingolipid homeostasis impacts the development and intergenerational health of the nervous system.One-Sentence Summary An intestinal lipid prevents neurodegeneration across generations.Competing Interest StatementThe authors have declared no competing interest.