Differential Regulation of Adhesion and Phagocytosis of Resting and Activated Microglia by Dopamine

Yang, Fan; Chen, Zhilu; Pathak, Janak L.; Carneiro, Ana M. D.; Chung, Chang Y.

doi:10.3389/fncel.2018.00309

Cited by 53 publications

(58 citation statements)

References 63 publications

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“…CSF1R also activates Akt [11], and it induces ERK1/2-mediated signaling in microglia [9]. Akt [22,67] and ERK1/2 [19] are involved in the phagocytic process. However, the specific signaling molecules downstream of CSF1R participating in phagocytosis in microglia after brain ischemia, and the precise step(s) of the phagocytic process affected by CSFR1 remain to be identified.…”

Section: Discussionmentioning

confidence: 99%

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation

et al. 2018

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Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia. Electronic supplementary material The online version of this article (10.1007/s00401-018-1954-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation

et al. 2018

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“…Since microglial cells reside in the CNS, they are exposed to dopamine released by dopaminergic neural circuits of the CNS. In this regard, dopaminergic signaling has been reported to modulate different microglial functions, including their inflammatory activity (Yan et al, 2015;Dominguez-Meijide et al, 2017;Elgueta et al, 2017), migration (Farber et al, 2005), and cell adhesion (Fan et al, 2018). Accordingly, microglial cells express both dopamine D1-like and D2-like receptors (Farber et al, 2005;Huck et al, 2015).…”

Section: Dopaminergic Regulation Of Microglial Cellsmentioning

confidence: 99%

“…This is the case of the DRD2, whose expression is induced upon inflammatory stimulation of microglial cells following stroke (Huck et al, 2015). High dopamine levels attenuate the inflammatory activation of microglia by reducing the release of nitric oxide (Farber et al, 2005) and decreasing the extent of phagocytosis (Fan et al, 2018). It has been suggested that this process may be mediated by the stimulation of low-affinity dopamine receptors in these cells, including DRD1 and DRD2 (Dominguez-Meijide et al, 2017), leading to a reduction in the phosphorylation of ERK1/2 (Fan et al, 2018), and to the inhibition of the angiotensin type-1/NADPH-oxidase/superoxide axis (Dominguez-Meijide et al, 2017).…”

Section: Dopaminergic Regulation Of Microglial Cellsmentioning

confidence: 99%

“…High dopamine levels attenuate the inflammatory activation of microglia by reducing the release of nitric oxide (Farber et al, 2005) and decreasing the extent of phagocytosis (Fan et al, 2018). It has been suggested that this process may be mediated by the stimulation of low-affinity dopamine receptors in these cells, including DRD1 and DRD2 (Dominguez-Meijide et al, 2017), leading to a reduction in the phosphorylation of ERK1/2 (Fan et al, 2018), and to the inhibition of the angiotensin type-1/NADPH-oxidase/superoxide axis (Dominguez-Meijide et al, 2017). In the same direction, it has been described that DRD1-signaling in microglial cells induces the cAMP-mediated degradation of the NLRP3 inflammasome, thus exerting a potent anti-inflammatory effect in vivo (Yan et al, 2015).…”

Section: Dopaminergic Regulation Of Microglial Cellsmentioning

confidence: 99%

“…Moreover, microglial complement-dependent signaling pathway mediates elimination of D1-like receptors in the nucleus accumbens of adolescent male, leading to the development of social behavior changes in male rats (Kopec et al, 2018). In addition, the stimulation of the DRD2 in homeostatic microglial cells has been shown to attenuate the inflammatory response (Dominguez-Meijide et al, 2017) by increasing p38MAPK and reducing the number of cellular processes (Fan et al, 2018). Furthermore, indirect mechanisms involving DRD2-signaling in astrocytes and triggering anti-inflammatory effects on microglial cells have been described.…”

Section: Dopaminergic Regulation Of Microglial Cellsmentioning

confidence: 99%

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

Vidal

Pacheco

2020

Front. Pharmacol.

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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.

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Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

Furgiuele,

Pereira,

Martini

et al. 2023

Clin & Trans Imm

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Parkinson's disease (PD) is a neurodegenerative disease affecting 7–10 million people worldwide. Currently, there is no treatment available to prevent or delay PD progression, partially due to the limited understanding of the pathological events which lead to the death of dopaminergic neurons in the substantia nigra in the brain, which is known to be the cause of PD symptoms. The current available treatments aim at compensating dopamine (DA) deficiency in the brain using its precursor levodopa, dopaminergic agonists and some indirect dopaminergic agents. The immune system is emerging as a critical player in PD. Therefore, immune‐based approaches have recently been proposed to be used as potential antiparkinsonian agents. It has been well‐known that dopaminergic pathways play a significant role in regulating immune responses in the brain. Although dopaminergic agents are the primary antiparkinsonian treatments, their immune regulatory effect has yet to be fully understood. The present review summarises the current available evidence of the immune regulatory effects of DA and its mimics and discusses dopaminergic agents as antiparkinsonian drugs. Based on the current understanding of their involvement in the regulation of neuroinflammation in PD, we propose that targeting immune pathways involved in PD pathology could offer a better treatment outcome for PD patients.

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Differential Regulation of Adhesion and Phagocytosis of Resting and Activated Microglia by Dopamine

Cited by 53 publications

References 63 publications

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation

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

Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

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