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Research ArticleSpecial Section on Sexual Dimorphism in Neuroimmune Cells

Neuroimmune Mechanisms and Sex/Gender-Dependent Effects in the Pathophysiology of Mental Disorders

Alexandros G. Kokkosis and Stella E. Tsirka
Journal of Pharmacology and Experimental Therapeutics October 2020, 375 (1) 175-192; DOI: https://doi.org/10.1124/jpet.120.266163
Alexandros G. Kokkosis
Department of Pharmacological Sciences, Stony Brook University, Stony Brook New York
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Stella E. Tsirka
Department of Pharmacological Sciences, Stony Brook University, Stony Brook New York
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Abstract

Innate and adaptive immune mechanisms have emerged as critical regulators of CNS homeostasis and mental health. A plethora of immunologic factors have been reported to interact with emotion- and behavior-related neuronal circuits, modulating susceptibility and resilience to mental disorders. However, it remains unclear whether immune dysregulation is a cardinal causal factor or an outcome of the pathologies associated with mental disorders. Emerging variations in immune regulatory pathways based on sex differences provide an additional framework for discussion in these psychiatric disorders. In this review, we present the current literature pertaining to the effects that disrupted immune pathways have in mental disorder pathophysiology, including immune dysregulation in CNS and periphery, microglial activation, and disturbances of the blood-brain barrier. In addition, we present the suggested origins of such immune dysregulation and discuss the gender and sex influence of the neuroimmune substrates that contribute to mental disorders. The findings challenge the conventional view of these disorders and open the window to a diverse spectrum of innovative therapeutic targets that focus on the immune-specific pathophenotypes in neuronal circuits and behavior.

SIGNIFICANCE STATEMENT The involvement of gender-dependent inflammatory mechanisms on the development of mental pathologies is gaining momentum. This review addresses these novel factors and presents the accumulating evidence introducing microglia and proinflammatory elements as critical components and potential targets for the treatment of mental disorders.

Footnotes

    • Received March 10, 2020.
    • Accepted July 9, 2020.
  • This work was partially supported by American Heart Association predoctoral fellowship 19PRE34370044 (A.G.K.) and by National Institutes of Health National Institute of Mental Health [grant R01MH123093].

  • https://doi.org/10.1124/jpet.120.266163.

  • Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 375 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 375, Issue 1
1 Oct 2020
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Research ArticleSpecial Section on Sexual Dimorphism in Neuroimmune Cells

Neuroimmune Mechanisms and Sex Effects in Mental Disorders

Alexandros G. Kokkosis and Stella E. Tsirka
Journal of Pharmacology and Experimental Therapeutics October 1, 2020, 375 (1) 175-192; DOI: https://doi.org/10.1124/jpet.120.266163

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Research ArticleSpecial Section on Sexual Dimorphism in Neuroimmune Cells

Neuroimmune Mechanisms and Sex Effects in Mental Disorders

Alexandros G. Kokkosis and Stella E. Tsirka
Journal of Pharmacology and Experimental Therapeutics October 1, 2020, 375 (1) 175-192; DOI: https://doi.org/10.1124/jpet.120.266163
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  • Article
    • Abstract
    • Introduction
    • Neuroimmune Interactions in Brain Homeostasis
    • Involvement of Immune Dysregulation in Mental Disorders: An Evolutionary Perspective
    • Integrating Neuroimmune Systems in Mental Disorder Pathogenesis
    • Sex and Gender Differences in Immunoneuropsychiatry
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