Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation
The vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of mic...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1527842/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841527869140893696 |
|---|---|
| author | Makenna Gargus Benneth Ben-Azu Benneth Ben-Azu Antonia Landwehr Jaclyn Dunn Joseph P. Errico Marie-Ève Tremblay Marie-Ève Tremblay |
| author_facet | Makenna Gargus Benneth Ben-Azu Benneth Ben-Azu Antonia Landwehr Jaclyn Dunn Joseph P. Errico Marie-Ève Tremblay Marie-Ève Tremblay |
| author_sort | Makenna Gargus |
| collection | DOAJ |
| description | The vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of microglia, the resident innate immune cells of the brain, is associated with various neurodevelopmental disorders, including schizophrenia, attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), and epilepsy. While the mechanistic understanding linking the VN, microglia, and neurodevelopmental disorders remains incomplete, vagus nerve stimulation (VNS) may provide a better understanding of the VN’s mechanisms and act as a possible treatment modality. In this review we examine the VN’s important role in modulating the immune system through the inflammatory reflex, which involves the cholinergic anti-inflammatory pathway, which releases acetylcholine. Within the central nervous system (CNS), the direct release of acetylcholine can also be triggered by VNS. Homeostatic balance in the CNS is notably maintained by microglia. Microglia facilitate neurogenesis, oligodendrogenesis, and astrogenesis, and promote neuronal survival via trophic factor release. These cells also monitor the CNS microenvironment through a complex sensome, including groups of receptors and proteins enabling microglia to modify neuroimmune health and CNS neurochemistry. Given the limitations of pharmacological interventions for the treatment of neurodevelopmental disorders, this review seeks to explore the application of VNS as an intervention for neurodevelopmental conditions. Accordingly, we review the established mechanisms of VNS action, e.g., modulation of microglia and various neurotransmitter pathways, as well as emerging preclinical and clinical evidence supporting VNS’s impact on symptoms associated with neurodevelopmental disorders, such as those related to CNS inflammation induced by infections. We also discuss the potential of adapting non-invasive VNS for the prevention and treatment of these conditions. Overall, this review is intended to increase the understanding of VN’s potential for alleviating microglial dysfunction involved in schizophrenia, ADHD, ASD, and epilepsy. Additionally, we aim to reveal new concepts in the field of CNS inflammation and microglia, which could serve to understand the mechanisms of VNS in the development of new therapies for neurodevelopmental disorders. |
| format | Article |
| id | doaj-art-f8c85507254a401290aa14d494763616 |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-f8c85507254a401290aa14d4947636162025-01-15T06:10:33ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-01-011810.3389/fnins.2024.15278421527842Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammationMakenna Gargus0Benneth Ben-Azu1Benneth Ben-Azu2Antonia Landwehr3Jaclyn Dunn4Joseph P. Errico5Marie-Ève Tremblay6Marie-Ève Tremblay7Division of Medical Sciences, University of Victoria, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDepartment of Pharmacology, Faculty of Basic Medical Sciences, Delta State University, Abraka, NigeriaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaVagus Nerve Society, Atlantic Beach, FL, United StatesDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDepartment of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, CanadaThe vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of microglia, the resident innate immune cells of the brain, is associated with various neurodevelopmental disorders, including schizophrenia, attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), and epilepsy. While the mechanistic understanding linking the VN, microglia, and neurodevelopmental disorders remains incomplete, vagus nerve stimulation (VNS) may provide a better understanding of the VN’s mechanisms and act as a possible treatment modality. In this review we examine the VN’s important role in modulating the immune system through the inflammatory reflex, which involves the cholinergic anti-inflammatory pathway, which releases acetylcholine. Within the central nervous system (CNS), the direct release of acetylcholine can also be triggered by VNS. Homeostatic balance in the CNS is notably maintained by microglia. Microglia facilitate neurogenesis, oligodendrogenesis, and astrogenesis, and promote neuronal survival via trophic factor release. These cells also monitor the CNS microenvironment through a complex sensome, including groups of receptors and proteins enabling microglia to modify neuroimmune health and CNS neurochemistry. Given the limitations of pharmacological interventions for the treatment of neurodevelopmental disorders, this review seeks to explore the application of VNS as an intervention for neurodevelopmental conditions. Accordingly, we review the established mechanisms of VNS action, e.g., modulation of microglia and various neurotransmitter pathways, as well as emerging preclinical and clinical evidence supporting VNS’s impact on symptoms associated with neurodevelopmental disorders, such as those related to CNS inflammation induced by infections. We also discuss the potential of adapting non-invasive VNS for the prevention and treatment of these conditions. Overall, this review is intended to increase the understanding of VN’s potential for alleviating microglial dysfunction involved in schizophrenia, ADHD, ASD, and epilepsy. Additionally, we aim to reveal new concepts in the field of CNS inflammation and microglia, which could serve to understand the mechanisms of VNS in the development of new therapies for neurodevelopmental disorders.https://www.frontiersin.org/articles/10.3389/fnins.2024.1527842/fullvagus nerveacetylcholinemicroglianeurodevelopmental disordersvagus nerve stimulation |
| spellingShingle | Makenna Gargus Benneth Ben-Azu Benneth Ben-Azu Antonia Landwehr Jaclyn Dunn Joseph P. Errico Marie-Ève Tremblay Marie-Ève Tremblay Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation Frontiers in Neuroscience vagus nerve acetylcholine microglia neurodevelopmental disorders vagus nerve stimulation |
| title | Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation |
| title_full | Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation |
| title_fullStr | Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation |
| title_full_unstemmed | Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation |
| title_short | Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation |
| title_sort | mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders a focus on microglia and neuroinflammation |
| topic | vagus nerve acetylcholine microglia neurodevelopmental disorders vagus nerve stimulation |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1527842/full |
| work_keys_str_mv | AT makennagargus mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT bennethbenazu mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT bennethbenazu mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT antonialandwehr mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT jaclyndunn mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT josephperrico mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT marieevetremblay mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation AT marieevetremblay mechanismsofvagusnervestimulationforthetreatmentofneurodevelopmentaldisordersafocusonmicrogliaandneuroinflammation |