TY - JOUR TI - Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia AU - Kennedy, Lauritz AU - Glesaaen, Emilie R AU - Palibrk, Vuk AU - Pannone, Marco AU - Wang, Wei AU - Al-Jabri, Ali AU - Suganthan, Rajikala AU - Meyer, Niklas AU - Austbø, Marie Landa AU - Lin, Xiaolin AU - Bergersen, Linda H AU - Bjørås, Magnar AU - Rinholm, Johanne E A2 - Ivy, Autumn S A2 - Bronner, Marianne E A2 - Roy, Achira A2 - Rosenberg, Paul A VL - 11 PY - 2022 DA - 2022/08/09 SP - e76451 C1 - eLife 2022;11:e76451 DO - 10.7554/eLife.76451 UR - https://doi.org/10.7554/eLife.76451 AB - Neonatal cerebral hypoxia-ischemia (HI) is the leading cause of death and disability in newborns with the only current treatment being hypothermia. An increased understanding of the pathways that facilitate tissue repair after HI may aid the development of better treatments. Here, we study the role of lactate receptor HCAR1 in tissue repair after neonatal HI in mice. We show that HCAR1 knockout mice have reduced tissue regeneration compared with wildtype mice. Furthermore, proliferation of neural progenitor cells and glial cells, as well as microglial activation was impaired. Transcriptome analysis showed a strong transcriptional response to HI in the subventricular zone of wildtype mice involving about 7300 genes. In contrast, the HCAR1 knockout mice showed a modest response, involving about 750 genes. Notably, fundamental processes in tissue repair such as cell cycle and innate immunity were dysregulated in HCAR1 knockout. Our data suggest that HCAR1 is a key transcriptional regulator of pathways that promote tissue regeneration after HI. KW - lactate KW - hcar1 KW - hca1 KW - gpr81 KW - ischemia KW - neurogenesis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -