TY - JOUR T1 - An intestinal sphingolipid promotes neuronal health across generations JF - bioRxiv DO - 10.1101/2022.07.24.501274 SP - 2022.07.24.501274 AU - Wenyue Wang AU - Tessa Sherry AU - Xinran Cheng AU - Qi Fan AU - Rebecca Cornell AU - Jie Liu AU - Zhicheng Xiao AU - Roger Pocock Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/07/24/2022.07.24.501274.abstract N2 - 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. ER -