Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice

Liu, Cuiping; Zhang, Shibo; Shi, Hongwei; Zhou, Haicong; Zhuang, Junyi; Cao, Yiyang; Ward, Natalie; Wang, Jiao

doi:10.3390/brainsci12060709

Open AccessArticle

Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice

by

Cuiping Liu

¹,

Shibo Zhang

¹

,

Hongwei Shi

¹,

Haicong Zhou

¹,

Junyi Zhuang

¹,

Yiyang Cao

¹,

Natalie Ward

² and

Jiao Wang

^1,*

¹

Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China

²

Banner Ocotillo Medical Center, 1405 S Alma School Rd, Chandler, AZ 85286, USA

^*

Author to whom correspondence should be addressed.

Brain Sci. 2022, 12(6), 709; https://doi.org/10.3390/brainsci12060709

Submission received: 21 April 2022 / Revised: 25 May 2022 / Accepted: 27 May 2022 / Published: 30 May 2022

(This article belongs to the Topic Applications of Biomedical Technology and Molecular Biological Approach in Brain Diseases)

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Abstract

The microbiota-gut-brain axis has attracted significant attention with respect to studying the mechanisms of brain aging; however, the specific connection between gut microbiota and aging remains unclear. The abnormal expression and mutation of proteins belonging to the P4-ATPase family, including Atp11b, results in a variety of neurological diseases. The results of our analysis demonstrate that there was a shift in the abundance of certain gut microbiota in Atp11b-knockout (KO) mice. Specifically, there was an increase in pro-inflammatory bacteria that accelerate aging and a decrease in probiotics that delay aging. Consequently, an enhanced oxidative stress response was observed, which was characterized by a reduction in the superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) and reactive oxygen species (ROS) levels. In addition, our data demonstrate that there was a decrease in the number of cells in the dentate gyrus (DG) region of the hippocampus, and aggravation of aging-related pathological features such as senescence β-galactosidase (SA-β-Gal), p-HistoneH2AX (Ser139), and p16^INK4. Moreover, KO mice show typical aging-associated behavior, such as memory impairment and slow pain perception. Taken together, we demonstrate a possible mechanism of aging induced by gut microbiota in Atp11b-KO mice, which provides a novel perspective for the treatment of aging through the microbiota-gut-brain axis.

Keywords: microbiota-gut-brain axis; brain aging; gut microbiota; Atp11b; aging pathology

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MDPI and ACS Style

Liu, C.; Zhang, S.; Shi, H.; Zhou, H.; Zhuang, J.; Cao, Y.; Ward, N.; Wang, J. Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice. Brain Sci. 2022, 12, 709. https://doi.org/10.3390/brainsci12060709

AMA Style

Liu C, Zhang S, Shi H, Zhou H, Zhuang J, Cao Y, Ward N, Wang J. Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice. Brain Sciences. 2022; 12(6):709. https://doi.org/10.3390/brainsci12060709

Chicago/Turabian Style

Liu, Cuiping, Shibo Zhang, Hongwei Shi, Haicong Zhou, Junyi Zhuang, Yiyang Cao, Natalie Ward, and Jiao Wang. 2022. "Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice" Brain Sciences 12, no. 6: 709. https://doi.org/10.3390/brainsci12060709

APA Style

Liu, C., Zhang, S., Shi, H., Zhou, H., Zhuang, J., Cao, Y., Ward, N., & Wang, J. (2022). Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice. Brain Sciences, 12(6), 709. https://doi.org/10.3390/brainsci12060709

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Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice

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