Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia.
Lauritz KennedyEmilie R GlesaaenVuk PalibrkMarco PannoneWei WangAli Al-JabriRajikala SuganthanNiklas MeyerMarie Landa AustbøXiaolin LinLinda H BergersenMagnar BjøråsJohanne Egge RinholmPublished in: eLife (2022)
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.
Keyphrases
- cell cycle
- stem cells
- transcription factor
- high fat diet induced
- gene expression
- neuropathic pain
- inflammatory response
- cell proliferation
- pregnant women
- endothelial cells
- induced apoptosis
- signaling pathway
- genome wide
- magnetic resonance
- cardiac arrest
- magnetic resonance imaging
- type diabetes
- brain injury
- spinal cord
- spinal cord injury
- wild type
- cell death
- metabolic syndrome
- oxidative stress
- binding protein
- subarachnoid hemorrhage
- deep learning
- blood brain barrier
- preterm infants