The Cross-Talk Between the Dopaminergic and the Immune System Involved in Schizophrenia

Abstract

Dopamine is one of the neurotransmitters whose transmission is altered in a number of neural pathways in the brain of schizophrenic patients. Current evidence indicates that these alterations involve hyperactive dopaminergic transmission in mesolimbic areas, striatum, and hippocampus, whereas hypoactive dopaminergic transmission has been reported in the prefrontal cortex of schizophrenic patients. Consequently, schizophrenia is associated with several cognitive and behavioral alterations. Of note, the immune system has been found to collaborate with the central nervous system in a number of cognitive and behavioral functions, which are dysregulated in schizophrenia. Moreover, emerging evidence has associated schizophrenia and inflammation. Importantly, different lines of evidence have shown dopamine as a major regulator of inflammation. In this regard, dopamine might exert strong regulation in the activity, migration, differentiation, and proliferation of immune cells that have been shown to contribute to cognitive functions, including T-cells, microglial cells, and peripheral monocytes. Thereby, alterations in dopamine levels associated to schizophrenia might affect inflammatory response of immune cells and consequently some behavioral functions, including reference memory, learning, social behavior, and stress resilience. Altogether these findings support the involvement of an active cross-talk between the dopaminergic and immune systems in the physiopathology of schizophrenia. In this review we summarize, integrate, and discuss the current evidence indicating the involvement of an altered dopaminergic regulation of immunity in schizophrenia.

Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems

“…Because the data suggested that microglial cells might be intimately involved in the pathogenesis of schizophrenia [ 60 , 61 ], we explored potential alterations in the pro- ( MhcII , Cd40 , iNos , Il-1β , Tnf-α and Il-6 ) and anti-inflammatory ( Arg1 , Igf-1 , Tgf-β and Il-4 ) factors that are also considered microglial markers ( Figure 9 and Figure 10 ).…”

Early Adolescence Prefrontal Cortex Alterations in Female Rats Lacking Dopamine Transporter

“…More recently, investigations on PFC during postnatal development revealed that DA homeostasis is tightly regulated by astroglial cells at this stage [ 13 ], thus highlighting the importance that glial cells play in regulating DA signaling during development. Indeed, several studies have confirmed that DA can exert either anti-inflammatory or pro-inflammatory effects in human and in vivo models through dopamine receptor activation on astrocytes and microglia [ 61 , 62 , 63 ]. In this framework, we sought to investigate the effects of DAT ablation in the prelimbic PFC, responsible for cognitive processing [ 64 ], that could lead to glial pro-inflammatory process that might contribute to the underlying pathophysiology of female DAT+/− and DAT−/− rats during early adolescence.…”

Increased Macrophages and C1qA, C3, C4 Transcripts in the Midbrain of People With Schizophrenia

“…A further aspect that we have not explored in this work is the dopaminergic regulation of the immune system. Immune cells, including T and B lymphocytes, dendritic cells, natural killer cells, macrophages, and microglia, express dopamine receptors and thus increased dopamine, as proposed to occur in schizophrenia, may itself regulate inflammatory activity [reviewed in ( 71 )]. Indeed, studies have identified B and T cells in the cortex and hippocampus of some people with schizophrenia ( 72 , 73 ), and investigating the presence of other peripheral immune cells in the midbrain and how these cells may be influenced by changes to dopamine or with antipsychotics in schizophrenia, is of interest.…”