TY - JOUR
T1 - Heterogeneity of microglial proton channel in different brain regions and its relationship with aging
AU - Kawai, Takafumi
AU - Takao, Keizo
AU - Akter, Sharmin
AU - Abe, Manabu
AU - Sakimura, Kenji
AU - Miyakawa, Tsuyoshi
AU - Okamura, Yasushi
N1 - Funding Information:
We thank Ms. Yuko Furukawa and Ms. Yuka Miyoshi (Osaka University) and Ms. Tamaki Kise and Ms. Yumie Koshidaka (National Institute for Physiological Sciences) for their animal care and technical supports. We also thank Ms. Risa Mori‐Kreiner (Osaka University) for her critical reading of the manuscript. This study was supported by the Center for Medical Research and Education, Graduate School of Medicine, Osaka Univ. This study was also supported by planned collaborative project (National Institute for Physiological Sciences). This work was supported by Grants‐in‐Aid from JSPS (15K18575) and SENSHIN Medical Research Foundation to T.K., Grant‐in‐Aid for Scientific Research on Innovative Areas (15H05901) and JSPS (21229003, 25253016, 19H03401) to Y.O.
Funding Information:
We thank Ms. Yuko Furukawa and Ms. Yuka Miyoshi (Osaka University) and Ms. Tamaki Kise and Ms. Yumie Koshidaka (National Institute for Physiological Sciences) for their animal care and technical supports. We also thank Ms. Risa Mori-Kreiner (Osaka University) for her critical reading of the manuscript. This study was supported by the Center for Medical Research and Education, Graduate School of Medicine, Osaka Univ. This study was also supported by planned collaborative project (National Institute for Physiological Sciences). This work was supported by Grants-in-Aid from JSPS (15K18575) and SENSHIN Medical Research Foundation to T.K., Grant-in-Aid for Scientific Research on Innovative Areas (15H05901) and JSPS (21229003, 25253016, 19H03401) to Y.O. All experiments were conducted in compliance with the ARRIVE guidelines.
Publisher Copyright:
© 2021 International Society for Neurochemistry
PY - 2021/5
Y1 - 2021/5
N2 - The properties of microglia largely differ depending on aging as well as on brain regions. However, there are few studies that investigated the functional importance of such heterogeneous properties of microglia at the molecular level. Voltage-gated proton channel, Hv1/VSOP, could be one of the candidates which confers functional heterogeneity among microglia since it regulates brain oxidative stress in age-dependent manner. In this study, we found that Hv1/VSOP shows brain region-dependent heterogeneity of gene expression with the highest level in the striatum. We studied the importance of Hv1/VSOP in two different brain regions, the cerebral cortex and striatum, and examined their relationship with aging (using mice of different ages). In the cortex, we observed the age-dependent impact of Hv1/VSOP on oxidative stress, microglial morphology, and gene expression profile. On the other hand, we found that the age-dependent significance of Hv1/VSOP was less obvious in the striatum than the cortex. Finally, we performed a battery of behavioral experiments on Hv1/VSOP-deficient mice both at young and aged stages to examine the effect of aging on Hv1/VSOP function. Hv1/VSOP-deficient mice specifically showed a marked difference in behavior in light/dark transition test only at aged stages, indicating that anxiety state is altered in aged Hv1/VSOP mice. This study suggests that a combination of brain region heterogeneity and animal aging underscores the functional importance of Hv1/VSOP in microglia. (Figure presented.).
AB - The properties of microglia largely differ depending on aging as well as on brain regions. However, there are few studies that investigated the functional importance of such heterogeneous properties of microglia at the molecular level. Voltage-gated proton channel, Hv1/VSOP, could be one of the candidates which confers functional heterogeneity among microglia since it regulates brain oxidative stress in age-dependent manner. In this study, we found that Hv1/VSOP shows brain region-dependent heterogeneity of gene expression with the highest level in the striatum. We studied the importance of Hv1/VSOP in two different brain regions, the cerebral cortex and striatum, and examined their relationship with aging (using mice of different ages). In the cortex, we observed the age-dependent impact of Hv1/VSOP on oxidative stress, microglial morphology, and gene expression profile. On the other hand, we found that the age-dependent significance of Hv1/VSOP was less obvious in the striatum than the cortex. Finally, we performed a battery of behavioral experiments on Hv1/VSOP-deficient mice both at young and aged stages to examine the effect of aging on Hv1/VSOP function. Hv1/VSOP-deficient mice specifically showed a marked difference in behavior in light/dark transition test only at aged stages, indicating that anxiety state is altered in aged Hv1/VSOP mice. This study suggests that a combination of brain region heterogeneity and animal aging underscores the functional importance of Hv1/VSOP in microglia. (Figure presented.).
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U2 - 10.1111/jnc.15292
DO - 10.1111/jnc.15292
M3 - Article
C2 - 33404063
AN - SCOPUS:85100220407
VL - 157
SP - 624
EP - 641
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -