Role of DARPP-32 phosphorylation by Cdk5 in amplication of dopamine signaling

Aging animals develop hypertension when challenged with high salt diet due, in part, to desensitization of dopamine receptors (DR) in renal proximal tubules (RPT). We have demonstrated that NHERF1 associates with DR1 and Na-K ATPase (NKA) and is important for regulation of NKA in RPT. Preliminary data showed loss of NHERF1 expression in 22m old F344 rats. We hypothesized that loss of NHERF1 results in increased blood pressure (BP) and lack of natriuretic response to dopamine (DA) in aging animals. To address this hypothesis, Fischer Brown Norway (FBN) rats (1m, 4m, 12m, and 24m old) were fed diet containing 1% or 8% NaCl for one week and, BP was measured in anesthetized animals using an indwelling left femoral artery catheter. 8% NaCl did not increase BP in 1m or 4 month old rats. By contrast, 8% NaCl diet increased BP in 12m (84.3±3.5 vs 90.8±2.36) and 24m (73.5±7.58 vs 104±1.6) old animals. To determine if lack of NHERF1 is responsible for the increase in BP, we measured BP in 12 m old WT and NHERF1 KO mice. By contrast to WT mice, 8% NaCl diet did not increase BP in NHERF1 KO mice (84±4.9 vs 96.5±3.56 (WT) and 78.2±3.89 vs 81.8±9.2 (NHERF1 KO mice)). To confirm that NHERF1 is required for DA-mediated inhibition of NKA, NKA activity in primary proximal tubule cells (PTC) from young and old mice in culture was measured in the presence or absence of DA. DA decreased NKA activity in PTC from young animals (67.2±3.8 vs 32.7±5.3) but not in PTC from old animals. Transfection of NHERF1 restored NKA regulation by DA in PTC from old rats (58.4±4.2 vs 64.4±4.3 (in untransfected cells) 54.2±3.8 vs 31.1±3.4 (in NHERF1 transfected cells)). We conclude that NHERF1 regulates DA-mediated proximal tubule sodium handling; however, other factors modulate BP response to dietary sodium intake in young and old animals. The contribution of NHERF1 and dopamine signaling to sodium homeostasis requires further study.

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Abstract 1022: The role of dopamine signaling in prostate cancer disparities

10.1158/1538-7445.am2019-1022 ◽

2019 ◽

Author(s):

Isaiah R. Pickett ◽

Ava M. Boston ◽

Marwah M. Almathkour ◽

Camille Ragin ◽

Mehmet A. Bilen ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Disparities ◽

Dopamine Signaling

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Chronic stress in adolescence differentially affects cocaine vulnerability in adulthood in a selectively bred rat model of individual differences: role of accumbal dopamine signaling

Stress ◽

10.1080/10253890.2020.1790520 ◽

2020 ◽

pp. 1-10

Author(s):

Cigdem Aydin ◽

Karla Frohmader ◽

Michael Emery ◽

Peter Blandino Jr ◽

Huda Akil

Keyword(s):

Individual Differences ◽

Chronic Stress ◽

Rat Model ◽

Dopamine Signaling

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The role of dopamine in reward-related behavior: shining new light on an old debate

Journal of Neurophysiology ◽

10.1152/jn.00323.2020 ◽

2020 ◽

Vol 124 (2) ◽

pp. 309-311

Author(s):

Allan R. Wang ◽

Alexa Groome ◽

Lara Taniguchi ◽

Neir Eshel ◽

Brandon S. Bentzley

Keyword(s):

Reinforcement Learning ◽

Ventral Tegmental Area ◽

Incentive Salience ◽

Ventral Tegmental ◽

Dopamine Signaling

The role dopamine plays in reward-related behaviors has been debated for decades. Heymann et al. (Heymann G, Jo YS, Reichard KL, McFarland N, Chavkin C, Palmiter RD, Soden ME, Zweifel LS. Neuron 105: 909–920, 2020) identify subpopulations of dopamine-producing neurons that separately mediate reward association and motivation. Their results help demonstrate that dopamine signaling may partake in both reinforcement learning and incentive salience functions, instantiated by neuropeptide-defined subpopulations of the ventral tegmental area with different projection targets.

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Dopamine manipulations drive changes in information sampling in healthy volunteers

Journal of Psychopharmacology ◽

10.1177/0269881118822080 ◽

2019 ◽

Vol 33 (6) ◽

pp. 670-677

Author(s):

Raquel Vicario-Feliciano ◽

Rebekah L Wigton ◽

Thomas P White ◽

Sukhi S Shergill ◽

Bruno B Averbeck

Keyword(s):

Cognitive Process ◽

Dopamine Release ◽

Receptor Activation ◽

Choice Task ◽

Double Blind ◽

Information Sampling ◽

Dopamine Signaling ◽

Beads Task ◽

Choice Tasks

Background: Information sampling is the cognitive process of accumulating information before committing to a decision. Patients across numerous disorders show decreased information sampling relative to controls. Aims: Here, we used the Beads and the Best Choice Tasks to study the role of dopamine signaling in information sampling. Methods: Participants were given placebo, amisulpride, or ropinirole in each session, in a double-blind cross-over design. Results: We found that ropinirole (agonist) increased the number of beads drawn in the Beads Task specifically when participants faced a loss, and decreased the rank of the chosen option in the Best Choice Task. Conclusions: These effects are likely driven by a combination of effects at presynaptic D2 receptors, which affect dopamine release, and post-synaptic D2 receptors. Increased D2 relative to D1 receptor activation in the striatum leads to increased sampling in the loss condition in the Beads Task. It also leads to choice of a poorer ranked option in the Best Choice Task. Decreased D2 relative to D1 receptor activation leads to decreased sampling in the Beads Task in the loss condition.

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Dopamine signaling attenuated myocardial injury during endotoxemia

American Journal of BioMedicine ◽

10.18081/2333-5106/018-19-29 ◽

2018 ◽

Vol 6 (1) ◽

pp. 33-43

Author(s):

Mark Turler ◽

Shel Thoma

Keyword(s):

Mononuclear Cells ◽

Intraperitoneal Administration ◽

Enzyme Linked Immunosorbent Assay ◽

Tunel Staining ◽

Lv Function ◽

Myocardial Apoptosis ◽

D2 Antagonist ◽

Dopamine Signaling ◽

First Time

Myocardial depression is a well-recognized manifestation of organ dysfunction in sepsis, the direct protective effect of Dopamine on myocardial is still not clear. Here, we aimed to study whether Dopamine can directly protect myocardial from endotoxemia. To test that, we used adult C57/BL6 mice were treated with endotoxin (0.5 mg/kg, iv). Clozapine was administered as D2 antagonist, (intraperitoneal administration shortly before the model of sepsis). Electron microscopy, TUNEL staining, caspase-3 expression, and the Bcl-2/Bax ratio were used to measure myocardial apoptosis. Left ventricle (LV) function was assessed using a microcatheter system. Chemokines and cytokines in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium were examined using immunofluorescence staining. In conclusion, our results for the first time showed the role of Dopamine to directly protect myocardial from endotoxemia through attenuated proinflammatory cytokines and partly through inhibiting apoptosis.

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Endocannabinoid-Like Lipid Neuromodulators in the Regulation of Dopamine Signaling: Relevance for Drug Addiction

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2020.588660 ◽

2020 ◽

Vol 12 ◽

Author(s):

Claudia Sagheddu ◽

Larissa Helena Torres ◽

Tania Marcourakis ◽

Marco Pistis

Keyword(s):

Psychiatric Disorders ◽

Biological Activities ◽

Signaling System ◽

Physiological Processes ◽

Naturally Occurring ◽

The Family ◽

Complex Lipid ◽

The Central Nervous System ◽

Dopamine Signaling

The family of lipid neuromodulators has been rapidly growing, as the use of different -omics techniques led to the discovery of a large number of naturally occurring N-acylethanolamines (NAEs) and N-acyl amino acids belonging to the complex lipid signaling system termed endocannabinoidome. These molecules exert a variety of biological activities in the central nervous system, as they modulate physiological processes in neurons and glial cells and are involved in the pathophysiology of neurological and psychiatric disorders. Their effects on dopamine cells have attracted attention, as dysfunctions of dopamine systems characterize a range of psychiatric disorders, i.e., schizophrenia and substance use disorders (SUD). While canonical endocannabinoids are known to regulate excitatory and inhibitory synaptic inputs impinging on dopamine cells and modulate several dopamine-mediated behaviors, such as reward and addiction, the effects of other lipid neuromodulators are far less clear. Here, we review the emerging role of endocannabinoid-like neuromodulators in dopamine signaling, with a focus on non-cannabinoid N-acylethanolamines and their receptors. Mounting evidence suggests that these neuromodulators contribute to modulate synaptic transmission in dopamine regions and might represent a target for novel medications in alcohol and nicotine use disorder.

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Gut-Amygdala Interactions in Autism Spectrum Disorders: Developmental Roles via regulating Mitochondria, Exosomes, Immunity and microRNAs

Current Pharmaceutical Design ◽

10.2174/1381612825666191105102545 ◽

2020 ◽

Vol 25 (41) ◽

pp. 4344-4356 ◽

Cited By ~ 6

Author(s):

Moonsang Seo ◽

George Anderson

Keyword(s):

Autism Spectrum Disorders ◽

Gut Microbiome ◽

Brain Regions ◽

Autism Spectrum ◽

Brain Functioning ◽

Sensory Interactions ◽

Spectrum Disorders ◽

Dopamine Signaling ◽

Number Of Treatment

Background: Autism Spectrum Disorders (ASD) have long been conceived as developmental disorder. A growing body of data highlights a role for alterations in the gut in the pathoetiology and/or pathophysiology of ASD. Recent work shows alterations in the gut microbiome to have a significant impact on amygdala development in infancy, suggesting that the alterations in the gut microbiome may act to modulate not only amygdala development but how the amygdala modulates the development of the frontal cortex and other brain regions. Methods: This article reviews wide bodies of data pertaining to the developmental roles of the maternal and foetal gut and immune systems in the regulation of offspring brain development. Results: A number of processes seem to be important in mediating how genetic, epigenetic and environmental factors interact in early development to regulate such gut-mediated changes in the amygdala, wider brain functioning and inter-area connectivity, including via regulation of microRNA (miR)-451, 14-3-3 proteins, cytochrome P450 (CYP)1B1 and the melatonergic pathways. As well as a decrease in the activity of monoamine oxidase, heightened levels of in miR-451 and CYP1B1, coupled to decreased 14-3-3 act to inhibit the synthesis of N-acetylserotonin and melatonin, contributing to the hyperserotonemia that is often evident in ASD, with consequences for mitochondria functioning and the content of released exosomes. These same factors are likely to play a role in regulating placental changes that underpin the association of ASD with preeclampsia and other perinatal risk factors, including exposure to heavy metals and air pollutants. Such alterations in placental and gut processes act to change the amygdala-driven biological underpinnings of affect-cognitive and affect-sensory interactions in the brain. Conclusion : Such a perspective readily incorporates previously disparate bodies of data in ASD, including the role of the mu-opioid receptor, dopamine signaling and dopamine receptors, as well as the changes occurring to oxytocin and taurine levels. This has a number of treatment implications, the most readily applicable being the utilization of sodium butyrate and melatonin.

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