Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of 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 ima...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.890855/full |
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| author | Francesco Bellanti Vidyasagar Naik Bukke Archana Moola Rosanna Villani Caterina Scuderi Luca Steardo Gianmauro Palombelli Rossella Canese Sarah Beggiato Mario Altamura Gianluigi Vendemiale Gaetano Serviddio Tommaso Cassano |
| author_facet | Francesco Bellanti Vidyasagar Naik Bukke Archana Moola Rosanna Villani Caterina Scuderi Luca Steardo Gianmauro Palombelli Rossella Canese Sarah Beggiato Mario Altamura Gianluigi Vendemiale Gaetano Serviddio Tommaso Cassano |
| author_sort | Francesco Bellanti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T05:27:14Z |
| format | Article |
| id | doaj.art-eb4fc34b055b4d509b299e586c485c12 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T05:27:14Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-eb4fc34b055b4d509b299e586c485c122022-12-22T00:36:25ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-05-011410.3389/fnagi.2022.890855890855Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's DiseaseFrancesco Bellanti0Vidyasagar Naik Bukke1Archana Moola2Rosanna Villani3Caterina Scuderi4Luca Steardo5Gianmauro Palombelli6Rossella Canese7Sarah Beggiato8Mario Altamura9Gianluigi Vendemiale10Gaetano Serviddio11Tommaso Cassano12Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Rome, ItalyMRI Unit Core Facilities, Istituto Superiore di Sanità, Rome, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyThe 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.https://www.frontiersin.org/articles/10.3389/fnagi.2022.890855/fullglutamatemitochondriahippocampusfrontal cortexmicrodialysisAlzheimer's disease |
| spellingShingle | Francesco Bellanti Vidyasagar Naik Bukke Archana Moola Rosanna Villani Caterina Scuderi Luca Steardo Gianmauro Palombelli Rossella Canese Sarah Beggiato Mario Altamura Gianluigi Vendemiale Gaetano Serviddio Tommaso Cassano Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease Frontiers in Aging Neuroscience glutamate mitochondria hippocampus frontal cortex microdialysis Alzheimer's disease |
| title | Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease |
| title_full | Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease |
| title_fullStr | Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease |
| title_full_unstemmed | Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease |
| title_short | Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease |
| title_sort | effects of ultramicronized palmitoylethanolamide on mitochondrial bioenergetics cerebral metabolism and glutamatergic transmission an integrated approach in a triple transgenic mouse model of alzheimer s disease |
| topic | glutamate mitochondria hippocampus frontal cortex microdialysis Alzheimer's disease |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.890855/full |
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