Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia
Lauritz Kennedy,
Emilie R Glesaaen,
Vuk Palibrk,
Marco Pannone,
Wei Wang,
Ali Al-Jabri,
Rajikala Suganthan,
Niklas Meyer,
Marie Landa Austbø,
Xiaolin Lin,
Linda H Bergersen,
Magnar Bjørås,
Johanne E Rinholm
Affiliations
Lauritz Kennedy
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Emilie R Glesaaen
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Vuk Palibrk
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Marco Pannone
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Wei Wang
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Ali Al-Jabri
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Rajikala Suganthan
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Marie Landa Austbø
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway
Xiaolin Lin
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Linda H Bergersen
The Brain and Muscle Energy Group, Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway; Center for Healthy Aging, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Magnar Bjørås
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway; Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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.
