Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia
Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses ha...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1139357/full |
| _version_ | 1797826852134322176 |
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| author | Benneth Ben-Azu Benneth Ben-Azu Elisabetta C. del Re Elisabetta C. del Re Elisabetta C. del Re Jared VanderZwaag Micaël Carrier Matcheri Keshavan Matcheri Keshavan Mohammadparsa Khakpour Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay |
| author_facet | Benneth Ben-Azu Benneth Ben-Azu Elisabetta C. del Re Elisabetta C. del Re Elisabetta C. del Re Jared VanderZwaag Micaël Carrier Matcheri Keshavan Matcheri Keshavan Mohammadparsa Khakpour Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay |
| author_sort | Benneth Ben-Azu |
| collection | DOAJ |
| description | Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ. |
| first_indexed | 2024-04-09T12:38:53Z |
| format | Article |
| id | doaj.art-94de1b38e6b9453fa9a9afc9c176bc4e |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-09T12:38:53Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-94de1b38e6b9453fa9a9afc9c176bc4e2023-05-15T05:07:14ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-05-011710.3389/fncel.2023.11393571139357Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophreniaBenneth Ben-Azu0Benneth Ben-Azu1Elisabetta C. del Re2Elisabetta C. del Re3Elisabetta C. del Re4Jared VanderZwaag5Micaël Carrier6Matcheri Keshavan7Matcheri Keshavan8Mohammadparsa Khakpour9Marie-Ève Tremblay10Marie-Ève Tremblay11Marie-Ève Tremblay12Marie-Ève Tremblay13Marie-Ève Tremblay14Marie-Ève Tremblay15Division of Medical Sciences, University of Victoria, Victoria, BC, CanadaDepartment of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, NigeriaDepartment of Psychiatry, Harvard Medical School, Boston, MA, United StatesVA Boston Healthcare System, Brockton, MA, United StatesBeth Israel Deaconess Medical Center, Boston, MA, United StatesDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDepartment of Psychiatry, Harvard Medical School, Boston, MA, United StatesBeth Israel Deaconess Medical Center, Boston, MA, United StatesDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaAxe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC, CanadaDepartment of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, CanadaDepartment of Neurology and Neurosurgery, McGill University, Montréal, QC, CanadaDepartment of Molecular Medicine, Université Laval, Québec City, QC, Canada0Centre for Advanced Materials and Related Technology (CAMTEC), Institute on Aging and Lifelong Health (IALH), University of Victoria, Victoria, BC, CanadaBrain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ.https://www.frontiersin.org/articles/10.3389/fncel.2023.1139357/fullmicrogliamicrobiomeepigeneticsschizophreniaagingpsychobiotics |
| spellingShingle | Benneth Ben-Azu Benneth Ben-Azu Elisabetta C. del Re Elisabetta C. del Re Elisabetta C. del Re Jared VanderZwaag Micaël Carrier Matcheri Keshavan Matcheri Keshavan Mohammadparsa Khakpour Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Marie-Ève Tremblay Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia Frontiers in Cellular Neuroscience microglia microbiome epigenetics schizophrenia aging psychobiotics |
| title | Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia |
| title_full | Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia |
| title_fullStr | Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia |
| title_full_unstemmed | Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia |
| title_short | Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia |
| title_sort | emerging epigenetic dynamics in gut microglia brain axis experimental and clinical implications for accelerated brain aging in schizophrenia |
| topic | microglia microbiome epigenetics schizophrenia aging psychobiotics |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1139357/full |
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