Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia
Citation
Rinholm, Johanne Egge et al. (2022), Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia, Dryad, Dataset, https://doi.org/10.5061/dryad.8w9ghx3kw
Abstract
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.
Methods
Tissue samples from the subventricular zone and hippocampus in the ipsilateral (damaged) and contralateral (undamaged) hemispheres of mice were dissected 3 days after HI. The samples were snap-frozen in liquid N2 and stored at −80°C before RNA isolation. RNA isolation was performed using QIAGEN allprep kit, and final RNA was dissolved in MQ H2O and stored at −80°C. Paired-end sequencing was performed with the Illumina platform by BGI Tech Solutions (Hong Kong).
Usage notes
Each file name describes genotype, mouse number, tissue type, hemisphere and forward/reverse RNAseq.
Abbreviations and explanations:
HCAR = HCAR1 knockout (-/-)
WT = wildtype (HCAR1 +/+)
SVZ = subventricular zone
HC = hippocampus
IPSI = ipsilateral hemisphere (damaged from hypoxia-ischemia)
CONTRA = contralateral hemisphere (undamaged, used as control)
1 at the end of the file name = forward
2 at the end of the file name = reverse
Funding
Helse Sør-Øst RHF, Award: 2020042
Helse Sør-Øst RHF, Award: 2018050
Nasjonalforeningen for Folkehelsen, Award: 4841
Civitan Alzheimer Fond
Helse Sør-Øst RHF, Award: PhD Fellowship 2020042
Helse Sør-Øst RHF, Award: Career Grant 2018050
Nasjonalforeningen for Folkehelsen, Award: Postdoctoral Fellowship 4841
Civitan Norway