Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia

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.