Chauhan Rupali, Mohan Maneesh, Mannan Ashi, Devi Sushma, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
Int Immunopharmacol. 2025 May 27;156:114654. doi: 10.1016/j.intimp.2025.114654. Epub 2025 Apr 27.
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.
神经精神障碍是临床上具有神经学和精神病学特征的疾病，由脑功能障碍或脑外疾病的间接影响引起。神经精神障碍往往会影响情绪、心境和脑功能。越来越多的证据表明，这些疾病的病因不仅限于神经元异常，还扩展到包括炎症。虽然这些疾病的潜在机制仍处于起步阶段，但最近的数据突出了神经炎症在其病理生理学中的重要作用。神经炎症涉及神经组织内的炎症，其特征是中枢神经系统内星形胶质细胞、细胞因子、小胶质细胞和趋化因子的改变。细胞因子包括干扰素-γ、白细胞介素-1β、白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-8、白细胞介素-10和白细胞介素-12。本综述重点关注白细胞介素-12（IL-12），这是神经炎症的关键介质，及其在神经精神障碍中的潜在作用。IL-12促进神经炎症并影响神经递质系统。此外，它还影响下丘脑-垂体-肾上腺（HPA）轴，损害神经可塑性，并通过与Toll样受体（TLR）、Janus激酶-信号转导和转录激活因子（JAK-STAT）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）、糖原合成酶激酶-3（GSK-3）、N-甲基-D-天冬氨酸（NMDA）、丝裂原活化蛋白激酶（MAPK）、蛋白激酶C（PKC）、血管内皮生长因子受体（VEGFR）、Rho相关卷曲螺旋蛋白激酶（ROCK）和Wnt信号通路相互作用来激活小胶质细胞，并在神经精神障碍中发挥其作用。在本综述中，我们详述了支持IL-12致病作用的现有证据，并探讨了其促成这些疾病发生和发展的可能机制。本综述旨在通过阐明神经炎症与神经精神障碍之间的相互作用，提供可能有助于未来治疗策略的见解。
