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.

Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1+ cells were the main cells responsible for producing IFN-γ. Additionally, the results suggested that the active compounds in the insoluble fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin receptors on dendritic cells, and they activated signaling cascades such as MAPK, NF-κB, and Syk. These findings suggest that B. rapa L. is a potentially promising immuno-improving material, and it might be useful for preventing immunological disorders such as infections and cancers by activating innate immunity.

Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer.