Changes in innate and acquired immune responses in mice with targeted deletion of the dopamine transporter gene

Kavelaars, Annemieke; Cobelens, Pieter M.; Teunis, Marc; Heijnen, Cobi J.

doi:10.1016/j.jneuroim.2005.01.004

Cited by 52 publications

(36 citation statements)

References 25 publications

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“…Dopaminergic neurotransmission is involved in memory processing (Bergson et al, 2003;Kavelaars et al, 2005;Seeman, 1992). Some studies have demonstrated alteration in the expression of two proteins associated with regulation of the dopaminergic signaling: Dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) and neuronal calcium sensor (NCS-1), both key downstream effectors in transducing dopamine (DA) signaling.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Comim

Silva

Mina

et al. 2014

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Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis, and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems. Thus, the objective of this study is to evaluate the neuronal calcium sensor (NCS-1) and dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) expression as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in prefrontal cortex and hippocampus of rats 12, 24, and 48 h after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation procedure. After 12 and 24 h, there was an increase of NGF levels in hippocampus; and up to 48 h, a decrease of NCS-1 expression in prefrontal cortex, a decrease of BDNF levels in hippocampus and an increase of NGF levels in hippocampus. In conclusion, we believe that the low expression of NCS-1 in prefrontal cortex and low levels of BDNF in hippocampus may be associated with the pathophysiology of cognitive impairment during sepsis and a putative role of the dopaminergic system.

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Section: Introductionmentioning

confidence: 99%

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Comim

Silva

Mina

et al. 2014

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“…Dopaminergic neurotransmission is involved in many functions in mammalians [1][2][3][4], and dopamine-mediated neurotransmission imbalances are associated with several psychiatry illnesses, such as schizophrenia [5][6].…”

Section: Introductionmentioning

confidence: 99%

DARPP-32 and NCS-1 Expression is not Altered in Brains of Rats Treated with Typical or Atypical Antipsychotics

et al. 2007

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Dopamine-mediated neurotransmission imbalances are associated with several psychiatry illnesses, such as schizophrenia. Recently it was demonstrated that two proteins involved in dopamine signaling are altered in prefrontal cortex (PFC) of schizophrenic patients. DARPP-32 is a key downstream effector of intracellular signaling pathway and is downregulated in PFC of schizophrenic subjects. NCS-1 is a neuronal calcium sensor that can inhibit dopamine receptor D2 internalization and is upregulated in PFC of schizophrenic subjects. It is well known that dopamine D2 receptor is the main target of antipsychotic. Therefore, our purpose was to study if chronic treatment with typical or atypical antipsychotics induced alterations in DARPP-32 and NCS-1 expression in five brain regions: prefrontal cortex, hippocampus, striatum, cortex and cerebellum. We did not find any changes in DARPP-32 and NCS-1 protein expression in any brain region investigated.

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“…Impairment of these synergic interactions lead to disease progression and aberrant immune responses (26). DARs are constitutively expressed on both human and murine NK cells where they modulate cytotoxicity, as observed in rats with a hyperreactive dopaminergic system and impaired NK cell functional responses (8,(28)(29)(30). Despite this experimental evidence, very little is known about the phenotypic distribution of DARs or the effects of DA on the homeostasis and effector functions of human resting and activated NK cells.…”

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confidence: 99%

Dopamine Inhibits the Effector Functions of Activated NK Cells via the Upregulation of the D5 Receptor

Mikulak

Bozzo

Roberto

et al. 2014

The Journal of Immunology

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Several lines of evidence indicate that dopamine (DA) plays a key role in the cross-talk between the nervous and immune systems. In this study, we disclose a novel immune-regulatory role for DA: inhibition of effector functions of activated NK lymphocytes via the selective upregulation of the D5 dopaminergic receptor in response to prolonged cell stimulation with rIL-2. Indeed, engagement of this D1-like inhibitory receptor following binding with DA suppresses NK cell proliferation and synthesis of IFN-γ. The inhibition of IFN-γ production occurs through blocking the repressor activity of the p50/c-REL dimer of the NF-κB complex. Indeed, the stimulation of the D5 receptor on rIL-2–activated NK cells inhibits the binding of p50 to the microRNA 29a promoter, thus inducing a de novo synthesis of this miRNA. In turn, the increased levels of microRNA 29a were inversely correlated with the ability of NK cells to produce IFN-γ. Taken together, our findings demonstrated that DA switches off activated NK cells, thus representing a checkpoint exerted by the nervous system to control the reactivity of these innate immune effectors in response to activation stimuli and to avoid the establishment of chronic and pathologic inflammatory processes.

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Changes in innate and acquired immune responses in mice with targeted deletion of the dopamine transporter gene

Cited by 52 publications

References 25 publications

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

DARPP-32 and NCS-1 Expression is not Altered in Brains of Rats Treated with Typical or Atypical Antipsychotics

Dopamine Inhibits the Effector Functions of Activated NK Cells via the Upregulation of the D5 Receptor

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