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

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.

Stability, bactericidal activity, vitamin B6 activity and gastrointestinal absorption of benzoic acid esters of pyridoxine.

alpha 4-O-Benzoyl-pyridoxine (PN-4'MB) and alpha 5-O-benzoyl-pyridoxine (PN-5'MB) were hydrolyzed in 10% aqueous solution of acetone at pH 1-4. They were hydrolyzed obeying apparent first-order kinetics. In the pH range of 1-7, PN-4'MB was hydrolyzed 10 times faster than PN-5'-MB. At pH 7-12, an interconversion between the two derivatives was observed. They were bactericidal against Escherichia coli and Bacillus subtilis and prevented severe convulsions induced in mouse by 4'-methoxypyridoxine, a potent antagonist of vitamin B6. PN-4'MB was hydrolyzed with the homogenate of rat liver more easily than PN-5'MB. The metabolite of PN-MBs in man was identified as 4'-pyridoxic acid, i.e., a principal metabolite of PN, using high-performance liquid chromatography. The amount of urinary excretion of 4'-pyridoxic acid in 10 hr after oral administration of PN-4'MB or PN-5'MB was as large as that of PN.