Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia
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Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia. / Kennedy, Lauritz; Glesaaen, Emilie R.; Palibrk, Vuk; Pannone, Marco; Wang, Wei; Al-Jabri, Ali; Suganthan, Rajikala; Meyer, Niklas; Austbø, Marie Landa; Lin, Xiaolin; Bergersen, Linda H.; Bjørås, Magnar; Rinholm, Johanne E.
In: eLife, Vol. 11, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia
AU - Kennedy, Lauritz
AU - Glesaaen, Emilie R.
AU - Palibrk, Vuk
AU - Pannone, Marco
AU - Wang, Wei
AU - Al-Jabri, Ali
AU - Suganthan, Rajikala
AU - Meyer, Niklas
AU - Austbø, Marie Landa
AU - Lin, Xiaolin
AU - Bergersen, Linda H.
AU - Bjørås, Magnar
AU - Rinholm, Johanne E.
N1 - Publisher Copyright: © 2022, Kennedy, Glesaaen et al.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - cell biology
KW - gpr81
KW - hca1
KW - hcar1
KW - ischemia
KW - lactate
KW - mouse
KW - neurogenesis
KW - neuroscience
U2 - 10.7554/eLife.76451
DO - 10.7554/eLife.76451
M3 - Journal article
C2 - 35942676
AN - SCOPUS:85135553182
VL - 11
JO - eLife
JF - eLife
SN - 2050-084X
ER -
ID: 316886494