Unlocking the Power of um-PEA: Mitochondrial Energy Boost and Brain Rescue

Published on May 24, 2022

In a world where energy is everything, the superhero known as um-PEA swoops in to save the day for mice with Alzheimer’s-like symptoms! These mice, known as triple transgenic (3 × Tg-AD) mice, received a special treatment of um-PEA for three months. The results? Mitochondrial bioenergetics and ATP production in the frontal cortex were miraculously improved! However, um-PEA couldn’t quite rescue the hippocampus, which suffered from metabolic and glutamate-related issues. Nonetheless, this study provided valuable insight into the effects of um-PEA on mouse brain metabolism and highlighted the discrepancy between cortical and hippocampal responses. Interestingly, age and disease progression were found to play a significant role in metabolism changes, further aligning with what we observe in human Alzheimer’s cases. So, while um-PEA made a heroic effort to save the day, there is still much to understand about its full potential in combating Alzheimer’s disease.

The therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) was investigated in young (6-month-old) and adult (12-month-old) 3 × Tg-AD mice, which received um-PEA for 3 months via a subcutaneous delivery system. Mitochondrial bioenergetics, ATP homeostasis, and magnetic resonance imaging/magnetic resonance spectroscopy were evaluated in the frontal cortex (FC) and hippocampus (HIPP) at the end of um-PEA treatment. Glutamate release was investigated by in vivo microdialysis in the ventral HIPP (vHIPP). We demonstrated that chronic um-PEA treatment ameliorates the decrease in the complex-I respiration rate and the FoF1-ATPase (complex V) activity, as well as ATP content depletion in the cortical mitochondria. Otherwise, the impairment in mitochondrial bioenergetics and the release of glutamate after depolarization was not ameliorated by um-PEA treatment in the HIPP of both young and adult 3 × Tg-AD mice. Moreover, progressive age- and pathology-related changes were observed in the cortical and hippocampal metabolism that closely mimic the alterations observed in the human AD brain; these metabolic alterations were not affected by chronic um-PEA treatment. These findings confirm that the HIPP is the most affected area by AD-like pathology and demonstrate that um-PEA counteracts mitochondrial dysfunctions and helps rescue brain energy metabolism in the FC, but not in the HIPP.

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