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

Abstract:

:Ascorbate, the reduced form of vitamin C, is highly concentrated in the central nervous system (CNS), including the retina, where it plays important physiological functions. In the CNS, the plasma membrane transporter sodium vitamin C co-transporter 2 (SVCT2) is responsible for ascorbate transport in neurons. The neurotransmitter dopamine (DA), acting through D1- and D2-like receptor subfamilies and classically coupled to adenylyl cyclase, is known to modulate synaptic transmission in the retina. Here, we reveal that DA controls the release of ascorbate from retinal neurons. Using primary retinal cultures, we show that this DA effect is dose-dependent, occurring by the reversal of the SVCT2, and could be elicited by brief and repetitive pulses of DA. The DA effect in inducing ascorbate release occurs by the activation of D1R and is independent of PKA. Moreover, the exchange protein directly activated by cAMP type 2 (EPAC2) is present in retinal neurons and its specific knockdown using shRNAs abrogates the D1R-induced ascorbate release. Confirming the physiological relevance of this pathway, activation of D1R or EPAC2 also triggered ascorbate release ex vivo in acute preparations of the intact retina. Overall, DA plays pivotal roles in regulating ascorbate homeostasis through an unanticipated signaling pathway involving D1R/adenylyl cyclase/cAMP/EPAC2, thereby suggesting that vitamin C might fine-tune dopaminergic neurotransmission in the retina.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

da Encarnação TG,Portugal CC,Nogueira CE,Santiago FN,Socodato R,Paes-de-Carvalho R

doi

10.1007/s12035-018-0962-7

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

7858-7871

issue

10

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-0962-7

journal_volume

55

pub_type

杂志文章
  • Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine).

    abstract::Dimebon (latrepirdine) is an anti-histaminergic agent which belongs to a fast-growing group of "old" medicines suggested to be of therapeutic utility for pathological conditions different from their original design ("repositioning"). Here, we overview the most recent studies on Dimebon directed to pathological process...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-015-9249-4

    authors: Ustyugov A,Shevtsova E,Bachurin S

    更新日期:2015-10-01 00:00:00

  • Atorvastatin Protects from Aβ1-40-Induced Cell Damage and Depressive-Like Behavior via ProBDNF Cleavage.

    abstract::Intracerebroventricular (icv) amyloid-beta (Aβ)1-40 infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predi...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0134-6

    authors: Ludka FK,Cunha MP,Dal-Cim T,Binder LB,Constantino LC,Massari CM,Martins WC,Rodrigues ALS,Tasca CI

    更新日期:2017-10-01 00:00:00

  • GTP-binding proteins and potassium channels involved in synaptic plasticity and learning.

    abstract::Inhibition of potassium channels is possibly the first step in the sequence of biochemical events leading to memory formation. These channels appear to be regulated directly or indirectly by GTP-binding proteins (G proteins), which may themselves be affected by phosphorylation and dephosphorylation in response to elev...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02935554

    authors: Nelson TJ,Alkon DL

    更新日期:1991-01-01 00:00:00

  • p38 MAPK Participates in the Mediation of GLT-1 Up-regulation During the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning.

    abstract::Our previous study has proved that the up-regulation of glial glutamate transporter 1 (GLT-1) played an important role in the acquisition of brain ischemic tolerance after cerebral ischemic preconditioning (CIP) in rats. However, little is known about the mechanism involved in the up-regulation of GLT-1 in the process...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9652-x

    authors: Zhang M,Gong JX,Wang JL,Jiang MY,Li L,Hu YY,Qi J,Zhang LY,Zhao H,Cui X,Xian XH,Li WB

    更新日期:2017-01-01 00:00:00

  • PGE2 Inhibits IL-10 Production via EP2-Mediated β-Arrestin Signaling in Neuroinflammatory Condition.

    abstract::Regulatory mechanisms of the expression of interleukin-10 (IL-10) in brain inflammatory conditions remain elusive. To address this issue, we used multiple primary brain cell cultures to study the expression of IL-10 in lipopolysaccharide (LPS)-elicited inflammatory conditions. In neuron-glia cultures, LPS triggered we...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8889-0

    authors: Chu CH,Chen SH,Wang Q,Langenbach R,Li H,Zeldin D,Chen SL,Wang S,Gao H,Lu RB,Hong JS

    更新日期:2015-08-01 00:00:00

  • Applying imaging genetics to ADHD: the promises and the challenges.

    abstract::Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood psychiatric disorders. During the past decades, studies have focused on its genetic background and the abnormality of the brain structure and function. Recently, an advanced technique linking these two areas, namely, the imaging gen...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-014-8683-z

    authors: Wu Z,Yang L,Wang Y

    更新日期:2014-10-01 00:00:00

  • Lipoprotein (a) as a Predictor of Early Stroke Recurrence in Acute Ischemic Stroke.

    abstract::Inflammation plays a crucial role in the pathogenesis of stroke. This study aims to determine lipoprotein (a) [Lp(a)] levels in serum and to investigate their associations with stroke recurrence events in a 3-month follow-up study in patients with acute ischemic stroke (AIS). Serum Lp(a) levels were determined in 203 ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0346-9

    authors: Hong XW,Wu DM,Lu J,Zheng YL,Tu WJ,Yan J

    更新日期:2018-01-01 00:00:00

  • Transcriptional Profiling of Individual Airway Projecting Vagal Sensory Neurons.

    abstract::Bronchopulmonary sensory neurons are derived from the vagal sensory ganglia and are essential for monitoring the physical and chemical environment of the airways and lungs. Subtypes are heterogenous in their responsiveness to stimuli, phenotype, and developmental origin, but they collectively serve to regulate normal ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-01782-8

    authors: Mazzone SB,Tian L,Moe AAK,Trewella MW,Ritchie ME,McGovern AE

    更新日期:2020-02-01 00:00:00

  • The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy.

    abstract::Astrogliosis and microgliosis in hippocampal sclerosis (HS) are widespread and are postulated to contribute to the pro-excitatory neuropathological environment. This study aimed to establish if seizure burden at the time of surgery or post-surgical outcome were correlated with the extent of gliosis in HS. As a seconda...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9465-y

    authors: Johnson AM,Sugo E,Barreto D,Hiew CC,Lawson JA,Connolly AM,Somerville E,Hasic E,Bye AM,Cunningham AM

    更新日期:2016-10-01 00:00:00

  • Tissue Transglutaminase and Its Product Isopeptide Are Increased in Alzheimer's Disease and APPswe/PS1dE9 Double Transgenic Mice Brains.

    abstract::Alzheimer's disease (AD) is characterized by intracellular and extracellular protein aggregates, including microtubule-associated protein tau and cleavage product of amyloid precursor protein, β-amyloid (Aβ). Tissue transglutaminase (tTG) is a calcium-dependent enzyme that cross-links proteins forming a γ-glutamyl-ε-l...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9413-x

    authors: Zhang J,Wang S,Huang W,Bennett DA,Dickson DW,Wang D,Wang R

    更新日期:2016-10-01 00:00:00

  • Activity-dependent changes in voltage-dependent calcium currents and transmitter release.

    abstract::Voltage-dependent Ca2+ channels are important in the regulation of neuronal structure and function, and as a result, they have received considerable attention. Recent studies have begun to characterize the diversity of their properties and the relationship of this diversity to their various cellular functions. In part...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02740620

    authors: Lnenicka GA,Hong SJ

    更新日期:1997-02-01 00:00:00

  • Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors.

    abstract::Conventional antidepressant drugs elevate the availability of monoamine neurotransmitters. However, these pharmacological therapies have limited efficacy and a slow onset of action as main limitations. New glutamatergic drugs such as ketamine have shown promise as a rapid-acting antidepressant drugs although with adve...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-01954-x

    authors: Gordillo-Salas M,Pascual-Antón R,Ren J,Greer J,Adell A

    更新日期:2020-08-01 00:00:00

  • Cytosolic Phospholipase A2 Facilitates Oligomeric Amyloid-β Peptide Association with Microglia via Regulation of Membrane-Cytoskeleton Connectivity.

    abstract::Cytosolic phospholipase A2 (cPLA2) mediates oligomeric amyloid-β peptide (oAβ)-induced oxidative and inflammatory responses in glial cells. Increased activity of cPLA2 has been implicated in the neuropathology of Alzheimer's disease (AD), suggesting that cPLA2 regulation of oAβ-induced microglial activation may play a...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1304-5

    authors: Teng T,Dong L,Ridgley DM,Ghura S,Tobin MK,Sun GY,LaDu MJ,Lee JC

    更新日期:2019-05-01 00:00:00

  • PLD3 in Alzheimer's disease.

    abstract::Rare coding variants in the phospholipase D3 (PLD3) gene, also known as HU-K4, have recently been identified to increase the risk for late-onset Alzheimer's disease (LOAD) by the whole exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large independent LOAD ca...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-014-8779-5

    authors: Wang J,Yu JT,Tan L

    更新日期:2015-04-01 00:00:00

  • Mechanotransduction: touch and feel at the molecular level as modeled in Caenorhabditis elegans.

    abstract::The survival of an organism depends on its ability to respond to its environment through its senses. The sense of touch is one of the most vital; still, it is the least understood. In the process of touch sensation, a mechanical stimulus is converted into electrical signals. Groundbreaking electrophysiological experim...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-007-8009-5

    authors: Bianchi L

    更新日期:2007-12-01 00:00:00

  • Effects of BDNF-Transfected BMSCs on Neural Functional Recovery and Synaptophysin Expression in Rats with Cerebral Infarction.

    abstract::The purpose of this study was to investigate the effects of brain-derived neurotrophic factor (BDNF)-transfected bone marrow mesenchymal stem cells (BMSCs) on neural functional recovery and synaptophysin expression in rats with cerebral infarction (CI). A total of 120 healthy Sprague Dawley rats were randomly divided ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9946-7

    authors: Zhang Y,Qiu B,Wang J,Yao Y,Wang C,Liu J

    更新日期:2017-07-01 00:00:00

  • Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis.

    abstract::Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,meta分析

    doi:10.1007/s12035-016-9823-4

    authors: Wu S,Han Y,Hu Q,Zhang X,Cui G,Li Z,Guan Y

    更新日期:2017-05-01 00:00:00

  • Phospholipase A2 in astrocytes: responses to oxidative stress, inflammation, and G protein-coupled receptor agonists.

    abstract::Astrocytes comprise the major cell type in the central nervous system (CNS) and they are essential for support of neuronal functions by providing nutrients and regulating cell-to-cell communication. Astrocytes also are immune-like cells that become reactive in response to neuronal injury. Phospholipases A2 (PLA2) are ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:31:1-3:027

    authors: Sun GY,Xu J,Jensen MD,Yu S,Wood WG,González FA,Simonyi A,Sun AY,Weisman GA

    更新日期:2005-01-01 00:00:00

  • Endoplasmic Reticulum Stress Plays a Key Role in Rotenone-Induced Apoptotic Death of Neurons.

    abstract::Rotenone, a pesticide, causes neurotoxicity via the mitochondrial complex-I inhibition. The present study was conducted to evaluate the role of endoplasmic reticulum (ER) stress in rotenone-induced neuronal death. Cell viability, cytotoxicity, reactive oxygen species (ROS) generation, nitrite level, mitochondrial memb...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-9001-5

    authors: Goswami P,Gupta S,Biswas J,Joshi N,Swarnkar S,Nath C,Singh S

    更新日期:2016-01-01 00:00:00

  • Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation.

    abstract::Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02802028

    authors: Tokuda M,Hatase O

    更新日期:1998-01-01 00:00:00

  • Progress in dodecafluoropentane emulsion as a neuroprotective agent in a rabbit stroke model.

    abstract::Dodecafluoropentane emulsion (DDFPe) in 250 nm nanodroplets seems to swell modestly to accept and carry large amounts of oxygen in the body at >29 °C. Small particle size allows oxygen delivery even into hypoxic tissue unreachable by erythrocytes. Using permanent cerebral embolic occlusion in rabbits, we assessed DDFP...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-013-8495-6

    authors: Woods SD,Skinner RD,Ricca AM,Brown AT,Lowery JD,Borrelli MJ,Lay JO,Culp WC

    更新日期:2013-10-01 00:00:00

  • Bexarotene Modulates Retinoid-X-Receptor Expression and Is Protective Against Neurotoxic Endoplasmic Reticulum Stress Response and Apoptotic Pathway Activation.

    abstract::Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription factor family of nuclear receptors that have gained recent research focus as potential targets for neurodegenerative disorders. Bexarotene is an RXR pharmacological agonist that is shown to be neuroprotective through its effects in promoting...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1041-9

    authors: Dheer Y,Chitranshi N,Gupta V,Abbasi M,Mirzaei M,You Y,Chung R,Graham SL,Gupta V

    更新日期:2018-12-01 00:00:00

  • The role of endozepine in the regulation of steroid synthesis.

    abstract::Endozepine has recently been isolated from various steroid-forming organs. The following article explores the role of endozepine in the regulation of steroid synthesis. Steroid hormone synthesis from cholesterol begins in the inner mitochondrial membrane, where cytochrome P450 converts cholesterol to pregnenolone. Sci...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02740835

    authors: Hall PF

    更新日期:1995-02-01 00:00:00

  • Protein Kinase C Regulates ASIC1a Protein Expression and Channel Function via NF-kB Signaling Pathway.

    abstract::Tissue acidosis is a common feature in many pathological conditions. Activation of acid-sensing ion channel 1a (ASIC1a) plays a key role in acidosis-mediated neurotoxicity. Protein kinase C (PKC) activity has been proved to be associated with many physiological processes and pathological conditions; however, whether P...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02056-4

    authors: Zhang L,Leng TD,Yang T,Li J,Xiong ZG

    更新日期:2020-11-01 00:00:00

  • New Insights into the Role of Ferritin in Iron Homeostasis and Neurodegenerative Diseases.

    abstract::Growing evidence has indicated that iron deposition is one of the key factors leading to neuronal death in the neurodegenerative diseases. Ferritin is a hollow iron storage protein composed of 24 subunits of two types, ferritin heavy chain (FTH) and ferritin light chain (FTL), which plays an important role in maintain...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-020-02277-7

    authors: Zhang N,Yu X,Xie J,Xu H

    更新日期:2021-01-28 00:00:00

  • Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice.

    abstract::Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9182-6

    authors: Freitas AE,Egea J,Buendia I,Gómez-Rangel V,Parada E,Navarro E,Casas AI,Wojnicz A,Ortiz JA,Cuadrado A,Ruiz-Nuño A,Rodrigues ALS,Lopez MG

    更新日期:2016-07-01 00:00:00

  • Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury.

    abstract::Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzym...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9118-1

    authors: Chen X,Chen X,Huang X,Qin C,Fang Y,Liu Y,Zhang G,Pan D,Wang W,Xie M

    更新日期:2016-04-01 00:00:00

  • A short history of LIM domains (1993-2002): from protein interaction to degradation.

    abstract::The LIM domain is a cysteine-rich zinc-finger motif found in a large family of proteins. In LIM-homeodomain (LIM-hd) transcription factors and LIM-only (LMO) factors, the LIM domains are responsible for key interactions with co-activators, co-repressors, competitors, and other transcription factors, and are therefore ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:26:2-3:269

    authors: Rétaux S,Bachy I

    更新日期:2002-10-01 00:00:00

  • Prioritizing Genes Related to Nicotine Addiction Via a Multi-source-Based Approach.

    abstract::Nicotine has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unknown....

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8874-7

    authors: Liu X,Liu M,Li X,Zhang L,Fan R,Wang J

    更新日期:2015-08-01 00:00:00

  • Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons.

    abstract::We have previously shown that inadequate dystrophin in cortical neurons in mdx mice is associated with age-dependent dyshomeostasis of resting intracellular Ca2+ ([Ca2+]i) and Na+ ([Na+]i), elevated reactive oxygen species (ROS) production, increase in neuronal damage and cognitive deficit. In this study, we assessed ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1018-8

    authors: Lopez JR,Uryash A,Kolster J,Estève E,Zhang R,Adams JA

    更新日期:2018-11-01 00:00:00