Prostaglandin D2 synthase controls Schwann cells metabolism
We previously reported that in the absence of Prostaglandin D2 synthase (LPGDS) peripheral nerves are hypomyelinated in development and that with aging they present aberrant myelin sheaths. We now demonstrate that glial LPGDS is part of a coordinated program that preserves myelin integrity. In vivo and in vitro lipidomic, metabolomic and transcriptomic analyses confirmed that myelin lipids composition, Schwann cells energetic metabolism and key enzymes controlling these processes are altered in the absence of LPGDS. Moreover, Schwann cells undergo a metabolic rewiring and turn to acetate as the main energetic source. Further, they produce ketone bodies to ensure glial cell and neuronal survival, describing the first physiological pathway implicated in preserving PNS myelin. All these changes correlate with morphological myelin alterations. We posit that myelin lipids serve as a reservoir to provide ketone bodies, which together with acetate represent the adaptive substrates Schwann cells can rely on to sustain the axoglial unit and preserve PNS integrity.