Enriched oxygen improves age-related cognitive impairment through enhancing autophagy

作者全名："Wang, Shengyuan; Chen, Bengang; Yuan, Minghao; Liu, Shu; Fan, Haixia; Yang, Xu; Zou, Qian; Pu, Yinshuang; Cai, Zhiyou"

作者地址："[Wang, Shengyuan; Yuan, Minghao; Liu, Shu; Fan, Haixia; Cai, Zhiyou] Chongqing Med Univ, Chongqing, Peoples R China; [Wang, Shengyuan; Chen, Bengang; Yuan, Minghao; Liu, Shu; Fan, Haixia; Cai, Zhiyou] Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing, Peoples R China; [Wang, Shengyuan; Chen, Bengang; Yuan, Minghao; Liu, Shu; Fan, Haixia; Yang, Xu; Zou, Qian; Pu, Yinshuang; Cai, Zhiyou] Univ Chinese Acad Sci, Chongqing Sch, Chongqing, Peoples R China; [Wang, Shengyuan; Chen, Bengang; Yuan, Minghao; Liu, Shu; Fan, Haixia; Yang, Xu; Zou, Qian; Pu, Yinshuang; Cai, Zhiyou] Chongqing Gen Hosp, Dept Neurol, Chongqing, Peoples R China"

通信作者："Cai, ZY (通讯作者)，Chongqing Med Univ, Chongqing, Peoples R China.; Cai, ZY (通讯作者)，Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing, Peoples R China.; Cai, ZY (通讯作者)，Univ Chinese Acad Sci, Chongqing Sch, Chongqing, Peoples R China.; Cai, ZY (通讯作者)，Chongqing Gen Hosp, Dept Neurol, Chongqing, Peoples R China."

来源：FRONTIERS IN AGING NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001174579300001

JCR分区：Q2

影响因子：4.1

年份：2024

卷号：16

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：hyperbaric oxygen therapy; autophagy; AMPK-mTOR pathway; tau hyperphosphorylation; cognitive impairment

摘要："Age-related cognitive impairment represents a significant health concern, with the understanding of its underlying mechanisms and potential interventions being of paramount importance. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) on cognitive function and neuronal integrity in aged (22-month-old) C57BL/6 mice. Male mice were exposed to HBOT for 2 weeks, and spatial learning and memory abilities were assessed using the Morris water maze. We employed transcriptome sequencing and Gene Ontology (GO) term enrichment analysis to examine the effects of HBOT on gene expression profiles, with particular attention given to synapse-related genes. Our data indicated a significant upregulation of postsynapse organization, synapse organization, and axonogenesis GO terms, likely contributing to improved cognitive performance. Moreover, the hyperphosphorylation of tau, a hallmark of many neurodegenerative diseases, was significantly reduced in the HBO-treated group, both in vivo and in vitro. Transmission electron microscopy revealed significant ultrastructural alterations in the hippocampus of the HBOT group, including an increase in the number of synapses and the size of the active zone, a reduction in demyelinated lesions, and a decreased number of ""PANTHOS."" Furthermore, Western blot analyses confirmed the upregulation of PSD95, BDNF, and Syn proteins, suggesting enhanced synaptic plasticity and neurotrophic support. Moreover, HBOT increased autophagy, as evidenced by the elevated levels of Beclin-1 and LC3 proteins and the reduced level of p62 protein. Finally, we demonstrated that HBOT activated the AMPK-mTOR signaling pathway, a critical regulator of autophagy. Notably, our findings provide novel insights into the mechanisms by which HBOT ameliorates age-related cognitive impairment, suggesting the potential therapeutic value of this approach."

基金机构：Foundation of Capacity Improvement in Neurology Department of Chongqing [ZS03174]; Construction Project of Capacity Improvement Plan for Chongqing Municipal Health Commission Affiliated Unit [ZS03174]; Chongqing Talent Project [2000079]; Overseas Students Entrepreneurial Fund [2000055]; Plan for High-level Talent Introduction [2019NLTS001]; [1000013]; [2000062]

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Foundation of Capacity Improvement in Neurology Department of Chongqing (ZS03174) and the Construction Project of Capacity Improvement Plan for Chongqing Municipal Health Commission Affiliated Unit (2019NLTS001)-ZS03174, the operating grant to Chongqing Key Laboratory of Neurodegenerative Diseases (1000013), Chongqing Talent Project (2000062), Overseas Students Entrepreneurial Fund (2000079), and Plan for High-level Talent Introduction (2000055)."