The Role of Lactylation in Mental Illness: Emphasis on Microglia
A paradigm shift is currently taking place in the etiopathogenesis of neuropsychiatric disorders as immunometabolism is replacing the earlier neurotransmitter model. According to the new concept, cellular bioenergetics drives information processing in the central nervous system; therefore, neuropath...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Neuroglia |
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| Online Access: | https://www.mdpi.com/2571-6980/4/2/9 |
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| author | Adonis Sfera Carolina Klein Johnathan J. Anton Zisis Kozlakidis Christina V. Andronescu |
| author_facet | Adonis Sfera Carolina Klein Johnathan J. Anton Zisis Kozlakidis Christina V. Andronescu |
| author_sort | Adonis Sfera |
| collection | DOAJ |
| description | A paradigm shift is currently taking place in the etiopathogenesis of neuropsychiatric disorders as immunometabolism is replacing the earlier neurotransmitter model. According to the new concept, cellular bioenergetics drives information processing in the central nervous system; therefore, neuropathology is conceptualized as a direct consequence of impaired metabolism. Along the same lines, endoplasmic reticulum stress and gut barrier dysfunction are emerging as novel targets in schizophrenia and affective disorders, linking immune responses to cellular distress. Furthermore, microglia, the brain’s innate immune cells, acquire energy through oxidative phosphorylation, while in the resting state, and glycolysis upon activation, contributing to lactate accumulation and reduced brain pH. The same metabolic signature characterizes neuropsychiatric disorders as the central nervous system derives adenosine triphosphate from aerobic glycolysis, upregulating lactate and generating an acidic environment. Although known for over three decades, the link between dysmetabolism and neuropathology was poorly defined until the discovery of brain-resident innate lymphoid cells, including natural killer cells, and lactylation of histone and nonhistone proteins. In this perspective article, we examine three anti-inflammatory microglial systems relevant for neuropsychiatry: lactate, oxytocin, and the aryl hydrocarbon receptor. We also discuss potential interventions for restoring microglial homeostasis. |
| first_indexed | 2024-03-11T02:05:31Z |
| format | Article |
| id | doaj.art-9b7a4a3c396b412cbca527218c6d701e |
| institution | Directory Open Access Journal |
| issn | 2571-6980 |
| language | English |
| last_indexed | 2024-03-11T02:05:31Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Neuroglia |
| spelling | doaj.art-9b7a4a3c396b412cbca527218c6d701e2023-11-18T11:54:33ZengMDPI AGNeuroglia2571-69802023-05-014211914010.3390/neuroglia4020009The Role of Lactylation in Mental Illness: Emphasis on MicrogliaAdonis Sfera0Carolina Klein1Johnathan J. Anton2Zisis Kozlakidis3Christina V. Andronescu4Patton State Hospital, Riverside, CA 92369, USANapa State Hospital, 2100 Napa Vallejo Hwy, Napa, CA 94558, USADepartment of Biomedical Sciences, California Baptist University, 8432 Magnolia Ave., Riverside, CA 92504, USAInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceDepartment of Cell Biology, Stanford University, 450 Serra Mall, Stanford, CA 94305, USAA paradigm shift is currently taking place in the etiopathogenesis of neuropsychiatric disorders as immunometabolism is replacing the earlier neurotransmitter model. According to the new concept, cellular bioenergetics drives information processing in the central nervous system; therefore, neuropathology is conceptualized as a direct consequence of impaired metabolism. Along the same lines, endoplasmic reticulum stress and gut barrier dysfunction are emerging as novel targets in schizophrenia and affective disorders, linking immune responses to cellular distress. Furthermore, microglia, the brain’s innate immune cells, acquire energy through oxidative phosphorylation, while in the resting state, and glycolysis upon activation, contributing to lactate accumulation and reduced brain pH. The same metabolic signature characterizes neuropsychiatric disorders as the central nervous system derives adenosine triphosphate from aerobic glycolysis, upregulating lactate and generating an acidic environment. Although known for over three decades, the link between dysmetabolism and neuropathology was poorly defined until the discovery of brain-resident innate lymphoid cells, including natural killer cells, and lactylation of histone and nonhistone proteins. In this perspective article, we examine three anti-inflammatory microglial systems relevant for neuropsychiatry: lactate, oxytocin, and the aryl hydrocarbon receptor. We also discuss potential interventions for restoring microglial homeostasis.https://www.mdpi.com/2571-6980/4/2/9microglianeuropathologylactylationoxytocinaryl hydrocarbon receptor |
| spellingShingle | Adonis Sfera Carolina Klein Johnathan J. Anton Zisis Kozlakidis Christina V. Andronescu The Role of Lactylation in Mental Illness: Emphasis on Microglia Neuroglia microglia neuropathology lactylation oxytocin aryl hydrocarbon receptor |
| title | The Role of Lactylation in Mental Illness: Emphasis on Microglia |
| title_full | The Role of Lactylation in Mental Illness: Emphasis on Microglia |
| title_fullStr | The Role of Lactylation in Mental Illness: Emphasis on Microglia |
| title_full_unstemmed | The Role of Lactylation in Mental Illness: Emphasis on Microglia |
| title_short | The Role of Lactylation in Mental Illness: Emphasis on Microglia |
| title_sort | role of lactylation in mental illness emphasis on microglia |
| topic | microglia neuropathology lactylation oxytocin aryl hydrocarbon receptor |
| url | https://www.mdpi.com/2571-6980/4/2/9 |
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