Dopamine Promotes Ascorbate Release from Retinal Neurons: Role of D1 Receptors and the Exchange Protein Directly Activated by cAMP type 2 (EPAC2)

Encarnação, Thaísa Godinho da; Portugal, Camila C.; Nogueira, Caio Eduardo; Santiago, Felipe N.; Socodato, Renato; Paes‐de‐Carvalho, Roberto

doi:10.1007/s12035-018-0962-7

Cited by 18 publications

(22 citation statements)

References 63 publications

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“…In addition, there is a certain amount of dopamine D1 receptors and GABA B Rs in the IC (Coffeen et al, 2010;Wu et al, 2017). Dopamine binds to D1 dopamine G protein-coupled receptors and activates an intracellular G-protein and then activates adenyl cyclase (AC) to produce cAMP (Da Encarnacão et al, 2018). cAMP binds to the regulatory domains of protein kinase A(PKA), causing the release of the effector domains (Sathler et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Postretrieval Microinjection of Baclofen Into the Agranular Insular Cortex Inhibits Morphine-Induced CPP by Disrupting Reconsolidation

Sun

Chang

et al. 2020

Front. Pharmacol.

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Environmental cues associated with drug abuse are powerful mediators of drug craving and relapse in substance-abuse disorders. Consequently, attenuating the strength of cuedrug memories could reduce the number of factors that cause drug craving and relapse. Interestingly, impairing cue-drug memory reconsolidation is a generally accepted strategy aimed at reducing the intensity of cues that trigger drug-seeking and drug-taking behaviors. In addition, the agranular insular cortex (AI) is an important component of the neural circuits underlying drug-related memory reconsolidation. GABA B receptors (GABA B Rs) are potential targets for the treatment of addiction, and baclofen (BLF) is the only prototypical GABA B agonist available for application in clinical addiction treatment. Furthermore, DFosB is considered a biomarker for the evaluation of potential therapeutic interventions for addiction. Here, we used the morphine-induced conditioned place preference (CPP) paradigm to investigate whether postretrieval microinjections of BLF into the AI could affect reconsolidation of drug-reward memory, reinstatement of CPP, and the level of DFosB in mice. Our results showed that BLF infused into the AI immediately following morphine CPP memory retrieval, but not 6 h postretrieval or following nonretrieval, could eliminate the expression of a morphine CPP memory. This effect persisted in a morphine-priming-induced reinstatement test, suggesting that BLF in the AI was capable of preventing the reconsolidation of the morphine CPP memory. Our results also showed that the elimination of morphine CPP memory was associated with reduced morphine-associated DFosB expression in the longer term. Taken together, the results of our research provide evidence to support that GABA B Rs in the AI have an important role in drug-cue memory reconsolidation and further our understanding of the role of the AI in drug-related learning and memory.

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Section: Discussionmentioning

confidence: 99%

Postretrieval Microinjection of Baclofen Into the Agranular Insular Cortex Inhibits Morphine-Induced CPP by Disrupting Reconsolidation

Sun

Chang

et al. 2020

Front. Pharmacol.

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“…The glutamate-induced ascorbate release is independent of calcium and mediated by the reversion of SVCT2 (Portugal et al, 2009). Moreover, by interacting with D 1 R and activating downstream EPAC2 pathway, DA induces ascorbate release also via SVCT2 reversion (da Encarnação et al, 2018). Because both the glutamatergic and the dopaminergic systems induce ascorbate release from neurons via the reversion of SVCT2, and the glutamatergic and dopaminergic systems are tightly associated in the retina, we studied whether the DA- and the glutamate-induced ascorbate release were, somehow, interconnected.…”

Section: Resultsmentioning

confidence: 99%

“…Although SVCTs are the major transporter systems regulating ascorbate uptake into cells, several mechanisms can be employed to mediate the release of ascorbate from cells (Corti et al, 2010). In one of such mechanisms, ascorbate can be released via the reversion of its high-affinity transporter SVCT2 (Portugal et al, 2009; da Encarnação et al, 2018). In neuronal cells, the neurotransmitters glutamate, acting on AMPA/kainate ionotropic receptors (Portugal et al, 2009), and dopamine (DA), acting through the D 1 R/cAMP/EPAC2 pathway (da Encarnação et al, 2018), can trigger SVCT2 reversion leading to ascorbate release.…”

Section: Introductionmentioning

confidence: 99%

“…In one of such mechanisms, ascorbate can be released via the reversion of its high-affinity transporter SVCT2 (Portugal et al, 2009; da Encarnação et al, 2018). In neuronal cells, the neurotransmitters glutamate, acting on AMPA/kainate ionotropic receptors (Portugal et al, 2009), and dopamine (DA), acting through the D 1 R/cAMP/EPAC2 pathway (da Encarnação et al, 2018), can trigger SVCT2 reversion leading to ascorbate release. Because both glutamate and DA (two major neurotransmitter systems in the CNS) promote SVCT2-induced ascorbate release from neurons, we asked if these two neurotransmitter systems were, somehow, linked to mediate the release of ascorbate.…”

Section: Introductionmentioning

confidence: 99%

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Dopamine-Induced Ascorbate Release From Retinal Neurons Involves Glutamate Release, Activation of AMPA/Kainate Receptors and Downstream Signaling Pathways

et al. 2019

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Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D 1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells.

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“…Dopamine, as a crucial neurotransmitter, can transmit neuronal signals to regulate neurological function by acting on specific dopamine receptors [ 1 , 2 ]. Currently, the dopamine receptor family is considered to play a key role in various advanced neural functions, including emotion, reward and autonomic movement [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway

Wang

Cui

et al. 2019

Acta Pharmacol Sin

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Microglia-mediated neuroinflammation is a crucial risk factor for neurological disorders. Recently, dopamine receptors have been found to be involved in multiple immunopathological processes and considered as valuable therapeutic targets for inflammation-associated neurologic diseases. In this study we investigated the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound isolated from medicinal plant Murraya exotica . We showed that isosibiricin (10−50 μM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-18 (IL-18). By using transcriptomics coupled with bioinformatics analysis, we revealed that isosibiricin treatment mainly affect dopamine receptor signalling pathway. We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 μM) or sultopride (1 μM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1β. Collectively, this study demonstrates a promising therapeutic strategy for neuroinflammation by targeting dopamine D1/2 receptors.

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Dopamine Promotes Ascorbate Release from Retinal Neurons: Role of D1 Receptors and the Exchange Protein Directly Activated by cAMP type 2 (EPAC2)

Cited by 18 publications

References 63 publications

Postretrieval Microinjection of Baclofen Into the Agranular Insular Cortex Inhibits Morphine-Induced CPP by Disrupting Reconsolidation

Postretrieval Microinjection of Baclofen Into the Agranular Insular Cortex Inhibits Morphine-Induced CPP by Disrupting Reconsolidation

Dopamine-Induced Ascorbate Release From Retinal Neurons Involves Glutamate Release, Activation of AMPA/Kainate Receptors and Downstream Signaling Pathways

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway

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