Kai Zhang1,2,3, Hiroshi Mizuma1,4, Yuka Nakatani1, Yousuke Kanayama1,4, Kayo Takahashi1, Yoshino Matsumoto1, Yasuhiro Wada1, Kayo Onoe1, Shino Owada1, Emi Hayashinaka1, Yuping Wu5, Xiaohui Zhang2, Mei Tian6, Hong Zhang7,8,9, Yasuyoshi Watanabe10. 1. Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan. 2. Department of Nuclear Medicine and PET-CT Centre, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. 3. International Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan. 4. Kavli Institute for the Physics and Mathematics of the Universe, The University of Tokyo, Kashiwa, Japan. 5. Laboratory for Biofunction Dynamics Imaging, RIKEN Centre for Biosystems Dynamics Research, Kobe, Japan. 6. Department of Nuclear Medicine and PET-CT Centre, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. meitian@zju.edu.cn. 7. Department of Nuclear Medicine and PET-CT Centre, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. hzhang21@zju.edu.cn. 8. Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China. hzhang21@zju.edu.cn. 9. College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China. hzhang21@zju.edu.cn. 10. Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan. yywata@riken.jp.
Abstract
PURPOSE: To investigate the in vivo neurofunctional changes and therapeutic effects of young blood plasma (YBP) in aged mice, as well as the molecular mechanisms underlying the therapeutic effects of YBP ex vivo and in vitro. METHODS: Aged C57/BL6 mice received systemic administrations of phosphate-buffered saline (PBS) or YBP twice a week, for 4 weeks. In vivo 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) under conscious state and cognitive behavioural tests were performed after 4-week treatment. In addition, an in vitro senescent model was established, and the expressions of key cognition-associated proteins and/or the alterations of key neuronal pathways were analysed in both brain tissues and cultured cells. RESULTS: Aged mice treated with YBP demonstrated higher glucose metabolism in the right hippocampus and bilateral somatosensory cortices, and lower glucose metabolism in the right bed nucleus of stria terminalis and left cerebellum. YBP treatment exerted beneficial effects on the spatial and long-term social recognition memory, and significantly increased the expressions of several cognition-related proteins and altered the key neuronal signalling pathways in the hippocampus and somatosensory cortex. Further in vitro studies suggested that YBP but not aged blood plasma significantly upregulated the expressions of several cognition-associated proteins. CONCLUSION: Our results highlight the role of the hippocampus and somatosensory cortex in YBP-induced beneficial effects on recognition memory in aged mice. 18F-FDG PET imaging under conscious state provides a new avenue for exploring the mechanisms underlying YBP treatment against age-related cognitive decline.
PURPOSE: To investigate the in vivo neurofunctional changes and therapeutic effects of young blood plasma (YBP) in aged mice, as well as the molecular mechanisms underlying the therapeutic effects of YBP ex vivo and in vitro. METHODS: Aged C57/BL6 mice received systemic administrations of phosphate-buffered saline (PBS) or YBP twice a week, for 4 weeks. In vivo 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) under conscious state and cognitive behavioural tests were performed after 4-week treatment. In addition, an in vitro senescent model was established, and the expressions of key cognition-associated proteins and/or the alterations of key neuronal pathways were analysed in both brain tissues and cultured cells. RESULTS: Aged mice treated with YBP demonstrated higher glucose metabolism in the right hippocampus and bilateral somatosensory cortices, and lower glucose metabolism in the right bed nucleus of stria terminalis and left cerebellum. YBP treatment exerted beneficial effects on the spatial and long-term social recognition memory, and significantly increased the expressions of several cognition-related proteins and altered the key neuronal signalling pathways in the hippocampus and somatosensory cortex. Further in vitro studies suggested that YBP but not aged blood plasma significantly upregulated the expressions of several cognition-associated proteins. CONCLUSION: Our results highlight the role of the hippocampus and somatosensory cortex in YBP-induced beneficial effects on recognition memory in aged mice. 18F-FDG PET imaging under conscious state provides a new avenue for exploring the mechanisms underlying YBP treatment against age-related cognitive decline.
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