精神障碍(MD)是非常普遍的,并且可能使人衰弱的复杂疾病,其原因仍然难以捉摸。研究这些疾病的病因或病理生理学的更深层次方面将是非常有益的,作为稀缺的知识在机械和分子途径肯定代表了一个重要的限制。MD和炎症/神经炎症之间的关联已被许多人广泛讨论和接受,据报道,在几个MD的患者中,有高水平的促炎细胞因子,如精神分裂症(SCZ),双相情感障碍(BD)和重度抑郁障碍(MDD),在其他人中。还报道了促炎标志物与症状强度的相关性。然而,在MD中观察到的炎症功能障碍的潜在机制尚未完全了解。在这种情况下,小胶质细胞功能障碍最近已经成为一个可能的关键因素,在神经炎症反应期间,小胶质细胞可以被过度激活,和过度产生促炎细胞因子,可以改变犬尿氨酸和谷氨酸信号,据报道。此外,小胶质细胞激活也导致增加的星形胶质细胞活性和随之而来的谷氨酸释放,它们都对中枢神经系统(CNS)有毒。此外,由于MD中的小胶质细胞活化增加,犬尿氨酸途径的产物显示出变化,然后影响多巴胺能,血清素能,和谷氨酸能信号通路。因此,在本次审查中,我们的目的是讨论神经炎症如何影响谷氨酸和犬尿氨酸信号通路,以及它们如何影响单胺能信号。随后还讨论了与MD主要症状的关联。因此,这项工作旨在通过提供对这些替代途径的见解,并通过揭示可能改善药物干预和/或治疗方案的策略以对抗MD的主要药理学上不匹配的症状的潜在靶标,从而为该领域做出贡献。作为SCZ。
Mental disorders (MDs) are highly prevalent and potentially debilitating complex disorders which causes remain elusive. Looking into deeper aspects of etiology or pathophysiology underlying these diseases would be highly beneficial, as the scarce knowledge in mechanistic and molecular pathways certainly represents an important limitation. Association between MDs and inflammation/neuroinflammation has been widely discussed and accepted by many, as high levels of pro-inflammatory cytokines were reported in patients with several MDs, such as schizophrenia (SCZ), bipolar disorder (BD) and major depression disorder (MDD), among others. Correlation of pro-inflammatory markers with symptoms intensity was also reported. However, the mechanisms underlying the inflammatory dysfunctions observed in MDs are not fully understood yet. In this context, microglial dysfunction has recently emerged as a possible pivotal player, as during the neuroinflammatory response, microglia can be over-activated, and excessive production of pro-inflammatory cytokines, which can modify the kynurenine and glutamate signaling, is reported. Moreover, microglial activation also results in increased astrocyte activity and consequent glutamate release, which are both toxic to the Central Nervous System (CNS). Also, as a result of increased microglial activation in MDs, products of the kynurenine pathway were shown to be changed, influencing then the dopaminergic, serotonergic, and glutamatergic signaling pathways. Therefore, in the present review, we aim to discuss how neuroinflammation impacts on glutamate and kynurenine signaling pathways, and how they can consequently influence the monoaminergic signaling. The consequent association with MDs main symptoms is also discussed. As such, this work aims to contribute to the field by providing insights into these alternative pathways and by shedding light on potential targets that could improve the strategies for pharmacological intervention and/or treatment protocols to combat the main pharmacologically unmatched symptoms of MDs, as the SCZ.