Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia
| Autor: | Emilie R Glesaaen, Lauritz Kennedy, 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 |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Mice
Knockout lactate General Immunology and Microbiology Neurogenesis General Neuroscience Brain hcar1 ischemia General Medicine General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled neuroscience neurogenesis Mice Animals Newborn Ischemia cell biology hca1 gpr81 Animals Lactic Acid Microglia Hypoxia mouse |
| Zdroj: | eLIFE Kennedy, L, Glesaaen, E R, Palibrk, V, Pannone, M, Wang, W, Al-Jabri, A, Suganthan, R, Meyer, N, Austbø, M L, Lin, X, Bergersen, L H, Bjørås, M & Rinholm, J E 2022, ' Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia ', eLife, vol. 11 . https://doi.org/10.7554/eLife.76451 |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.76451 |
| Popis: | 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.Hypoxic-ischaemic brain injury is the most common cause of disability in newborn babies. This happens when the blood supply to the brain is temporarily blocked during birth and cells do not receive the oxygen and nutrients they need to survive. Cooling the babies down after the hypoxic-ischemic attack (via a technique called hypothermic treatment) can to some extent reduce the damage caused by the injury. However, doctors still need new drugs that can protect the brain and improve its recovery after the injury has occurred. Research in mice suggests that a chemical called lactate might help the brain to recover. Lactate is produced by muscles during hard exercise to provide energy to cells when oxygen levels are low |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|