Neural correlates of beneficial effects of young plasma treatment in aged mice: PET-SPM analyses and neuro-behavioural/molecular biological studies

• Published in: European journal of nuclear medicine and molecular imaging Vol. 49; no. 5; pp. 1456 - 1469
• Main Authors: Zhang, Kai, Mizuma, Hiroshi, Nakatani, Yuka, Kanayama, Yousuke, Takahashi, Kayo, Matsumoto, Yoshino, Wada, Yasuhiro, Onoe, Kayo, Owada, Shino, Hayashinaka, Emi, Wu, Yuping, Zhang, Xiaohui, Tian, Mei, Zhang, Hong, Watanabe, Yasuyoshi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2022; Springer Nature B.V
• Subjects: Age; Animals; Blood plasma; Brain - diagnostic imaging; Brain - metabolism; Cardiology; Cerebellum; Cognition; Cognition & reasoning; Cognitive ability; Consciousness; Cortex (somatosensory); Emission analysis; Fluorine isotopes; Fluorodeoxyglucose F18 - metabolism; Glucose; Glucose - metabolism; Hippocampus; Humans; Imaging; In vitro methods and tests; In vivo methods and tests; Medicine; Medicine & Public Health; Memory; Metabolism; Mice; Molecular modelling; Neuroimaging; Nuclear Medicine; Oncology; Original Article; Orthopedics; Plasma; Plasma - metabolism; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Preclinical Imaging; Proteins; Radiology; Recognition; Signal transduction; Social interactions; Stria terminalis; Tomography; Tomography, X-Ray Computed; Aging; Positron emission tomography (PET); Young blood plasma; Cognition; Conscious; Memory
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05598-4

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-[ 18 F]-fluoro-2-deoxy- d -glucose positron emission tomography ( 18 F-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. 18 F-FDG PET imaging under conscious state provides a new avenue for exploring the mechanisms underlying YBP treatment against age-related cognitive decline.