The emerging neuroimmune hypothesis of bipolar disorder: An updated overview of neuroimmune and microglial findings

dc.contributor.authorChaves-Filho, Adriano José Maia
dc.contributor.authorEyres, Capri
dc.contributor.authorBlöbaum, Leonie
dc.contributor.authorLandwehr, Antonia
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2024-06-17T16:12:03Z
dc.date.available2024-06-17T16:12:03Z
dc.date.issued2024
dc.description.abstractBipolar disorder (BD) is a severe and multifactorial disease, with onset usually in young adulthood, which follows a progressive course throughout life. Replicated epidemiological studies have suggested inflammatory mechanisms and neuroimmune risk factors as primary contributors to the onset and development of BD. While not all patients display overt markers of inflammation, significant evidence suggests that aberrant immune signaling contributes to all stages of the disease and seems to be mood phase dependent, likely explaining the heterogeneity of findings observed in this population. As the brain's immune cells, microglia orchestrate the brain's immune response and play a critical role in maintaining the brain's health across the lifespan. Microglia are also highly sensitive to environmental changes and respond to physiological and pathological events by adapting their functions, structure, and molecular expression. Recently, it has been highlighted that instead of a single population of cells, microglia comprise a heterogeneous community with specialized states adjusted according to the local molecular cues and intercellular interactions. Early evidence has highlighted the contribution of microglia to BD neuropathology, notably for severe outcomes, such as suicidality. However, the roles and diversity of microglial states in this disease are still largely undermined. This review brings an updated overview of current literature on the contribution of neuroimmune risk factors for the onset and progression of BD, the most prominent neuroimmune abnormalities (including biomarker, neuroimaging, ex vivo studies) and the most recent findings of microglial involvement in BD neuropathology. Combining these different shreds of evidence, we aim to propose a unifying hypothesis for BD pathophysiology centered on neuroimmune abnormalities and microglia. Also, we highlight the urgent need to apply novel multi-system biology approaches to characterize the diversity of microglial states and functions involved in this enigmatic disorder, which can open bright perspectives for novel biomarkers and therapeutic discoveries.
dc.description.reviewstatusReviewed
dc.description.scholarlevelFaculty
dc.description.sponsorshipThis work was supported by a start-up grant from the Division of Medical Sciences, University of Victoria. Marie-Ève Tremblay is a Tier 2 Canada Research Chair in Neurobiology of Aging and Cognition (CRC-2019-00407). Adriano Chavez-Filho is supported by an Aspiration 2030 Postdoctoral Fellowship from the University of Victoria (2023–2025) and a Fellowship from the Women Health Research Insitute (2023–2024).
dc.identifier.citationChaves‐Filho, A., Eyres, C., Blöbaum, L., Landwehr, A., & Tremblay, M. (2024). The emerging neuroimmune hypothesis of bipolar disorder: An updated overview of neuroimmune and microglial findings. Journal of Neurochemistry. https://doi.org/10.1111/jnc.16098
dc.identifier.urihttps://doi.org/10.1111/jnc.16098
dc.identifier.urihttps://hdl.handle.net/1828/16615
dc.language.isoen
dc.publisherJournal of Neurochemistry
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectbipolar disorder
dc.subjectcytokines
dc.subjectinflammation
dc.subjectmicroglia
dc.subjectneuroimmune risk factors
dc.titleThe emerging neuroimmune hypothesis of bipolar disorder: An updated overview of neuroimmune and microglial findings
dc.typeArticle

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