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bioRxiv · 10.1101/2022.07.24.501274

An intestinal sphingolipid promotes neuronal health across generations

Wang, W.·Sherry, T.·Cheng, X.·Fan, Q.·Cornell, R.·Liu, J.·Xiao, Z.·Pocock, R.
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Abstract

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 SummaryAn intestinal lipid prevents neurodegeneration across generations.

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Wang, W., Sherry, T., Cheng, X., Fan, Q., Cornell, R., Liu, J., Xiao, Z., Pocock, R.. 2022-07-24. An intestinal sphingolipid promotes neuronal health across generations. https://doi.org/10.1101/2022.07.24.501274

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