Unravelling the role of Interleukin-12 in Neuroinflammatory mechanisms: Pathogenic pathways linking Neuroinflammation to neuropsychiatric disorders

Neuropsychiatric disorders are clinically characterized conditions involving both neurology and psychiatry, arising from dysfunctioning of cerebral function, or indirect effects of extra cerebral disease. Neuropsychiatric disorders tend to influence emotions, mood, and brain functioning. Growing evidence indicates that the etiology of these disorders is not confined to neuronal abnormalities but extends to include inflammation. While the underlying mechanism of these disorders is still in its infancy, recent data highlights the significant role of neuroinflammation in their pathophysiology. Neuroinflammation concerns the inflammation within the neural tissue characterized by alteration in astrocytes, cytokines, microglia, and chemokines within the central nervous system. The cytokines include IFN-γ, IL-1β, IL-2, IL4, IL-6, IL-8, IL-10, and IL-12. This review focuses on interleukin-12 (IL-12), a key mediator of neuroinflammation, and its potential involvement in neuropsychiatric disorders. IL-12 promotes neuroinflammation and influences neurotransmitter systems. Additionally, it also affects the HPA axis, impairs neuroplasticity, and activates microglia by interacting with TLR, JAK-STAT, PI3K/Akt, GSK-3, NMDA, MAPK, PKC, VEGFR, ROCK, and Wnt signaling pathways and elicit its role in ND. In this review, we dwell on the current evidence supporting IL-12's pathogenic role and explore the possible mechanisms by which it contributes to the development and progression of these conditions. This review aims to provide insights that may aid in future therapeutic strategies by illuminating the interplay between neuroinflammation and neuropsychiatric disorders.