Serine Racemase mediates subventricular zone neurogenesis via fatty acid metabolism

Robin Roychaudhuri, Hasti Atashi, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

The adult subventricular zone (SVZ) is a neurogenic niche that continuously produces newborn neurons. Here we show that serine racemase (SR), an enzyme that catalyzes the racemization of L-serine to D-serine and vice versa, affects neurogenesis in the adult SVZ by controlling de novo fatty acid synthesis. Germline and conditional deletion of SR (nestin precursor cells) leads to diminished neurogenesis in the SVZ. Nestin-cre+ mice showed reduced expression of fatty acid synthase and its substrate malonyl-CoA, which are involved in de novo fatty acid synthesis. Global lipidomic analyses revealed significant alterations in different lipid subclasses in nestin-cre+ mice. Decrease in fatty acid synthesis was mediated by phospho Acetyl-CoA Carboxylase that was AMP-activated protein kinase independent. Both L- and D-serine supplementation rescued defects in SVZ neurogenesis, proliferation, and levels of malonyl-CoA in vitro. Our work shows that SR affects adult neurogenesis in the SVZ via lipid metabolism.

Original languageEnglish (US)
Pages (from-to)1482-1499
Number of pages18
JournalStem Cell Reports
Volume18
Issue number7
DOIs
StatePublished - Jul 11 2023

Keywords

  • D-serine,
  • L-serine,
  • adult neurogenesis,
  • lipid metabolism,
  • malonyl-CoA
  • serine racemase,
  • subventricular zone,

ASJC Scopus subject areas

  • Genetics
  • Biochemistry
  • Cell Biology
  • Developmental Biology

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