dopaminergic system
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Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 145
Author(s):  
Qiujin Yan ◽  
Xiulin Wu ◽  
Ping Zhou ◽  
Yan Zhou ◽  
Xuhang Li ◽  
...  

An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A/AKT1/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia.


Author(s):  
Graham Music

In this article I describe those caught up in an increasingly common but worrying phenomenon, that of addictive states of mind, seen, for example, in obsessional use of video games or pornography. While the contemporary world has exacerbated the risks, addictive traits often originate in attempts to escape from an inner pain or deadness towards the false promise offered by the object of addiction. The article offers a different view of the dopaminergic system. It also looks at how the contemporary world is posing new challenges for people who have developed with such a propensity, and we will see how those prone to addictive states of mind struggle to bear certain emotional states, finding them overwhelming, and instead reach for a solution via their addiction.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Allison E Hamilos ◽  
Giulia Spedicato ◽  
Ye Hong ◽  
Fangmiao Sun ◽  
Yulong Li ◽  
...  

Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a role in motor control, but how the endogenous dopaminergic system influences movement is unknown. Here we examined the relationship between dopaminergic signaling and the timing of reward-related movements in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue; reward was delivered in response to movements initiated after a criterion time. The movement time was variable from trial-to-trial, as expected from previous studies. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement/reward time on single trials. Steeply rising signals preceded early lick-initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movements. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of movement initiation, whereas inhibition caused late-shifting, as if modulating the probability of movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation on single trials. We propose that ramping dopaminergic signals, likely encoding dynamic reward expectation, can modulate the decision of when to move.


2021 ◽  
Vol 12 ◽  
Author(s):  
Heinz Grunze ◽  
Réka Csehi ◽  
Christoph Born ◽  
Ágota Barabássy

The dopaminergic system plays a central and decisive role in substance use disorder (SUD), bipolar disorder (BD), and possibly in a subgroup of patients with refractory depression. Common genetic markers and underlying cellular processes, such as kindling, support the close link between these disorders, which is also expressed by the high rate of comorbidity. Although partial dopamine agonists/antagonists acting on D2 and D3 receptors have an established role in treating BD, their usefulness in SUD is less clear. However, dopamine D3 receptors were shown to play a central role in SUD and BD, making D2/D3 partial agonists/antagonists a potential target for both disorders. This narrative review examines whether these substances bear the promise of a future therapeutic approach especially in patients with comorbid BD and SUD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Oliver Grimm ◽  
Daan van Rooij ◽  
Asya Tshagharyan ◽  
Dilek Yildiz ◽  
Jan Leonards ◽  
...  

AbstractADHD is a neurodevelopmental disorder with a long trajectory into adulthood where it is often comorbid with depression, substance use disorder (SUD) or obesity. Previous studies described a dysregulated dopaminergic system, reflected by abnormal reward processing, both in ADHD as well as in depression, SUD or obesity. No study so far however tested systematically whether pathologies in the brain’s reward system explain the frequent comorbidity in adult ADHD. To test this, we acquired MRI scans from 137 participants probing the reward system by a monetary incentive delay task (MIDT) as well as assessing resting-state connectivity with ventral striatum as a seed mask. No differences were found between comorbid disorders, but a significant linear effect pointed toward less left intrastriatal connectivity in patients depending on the number of comorbidities. This points towards a neurobiologically impaired reward- and decision-making ability in patients with more comorbid disorders. This suggests that less intrastriatal connectivity parallels disorder severity but not disorder specificity, while MIDT abnormalities seem mainly to be driven by ADHD.


2021 ◽  
Vol 53 ◽  
pp. S182-S183
Author(s):  
K. Prasad ◽  
E. Van der Meiden ◽  
R. Moraga-Amaro ◽  
D.A. Vazquez-Matias ◽  
E.F.J. de Vries ◽  
...  

2021 ◽  
Vol 22 (23) ◽  
pp. 12932
Author(s):  
Magdalena Kurnik-Łucka ◽  
Paweł Pasieka ◽  
Patrycja Łączak ◽  
Marcin Wojnarski ◽  
Michał Jurczyk

Background: an increased prevalence of gastro-duodenal ulceration was described almost sixty years ago as prodromal to idiopathic Parkinson’s disease, while duodenal ulcers have been rarely diagnosed in patients with schizophrenia. The cytoprotective role of dopamine in animal models of gastrointestinal ulcerations has also been described. Interestingly, Parkinson’s disease (PD) might share common pathophysiological links with inflammatory bowel disease (IBD) as epidemiological and genetic links already suggest. Thus, the aim of our study was to review the existing literature on the role of the gastrointestinal dopaminergic system in IBD pathogenesis and progression. Methods: a systematic search was conducted according to the PRISMA methodology. Results: twenty-four studies satisfied the predetermined criteria and were included in our qualitative analysis. Due to different observations (cross-sectional studies) as well as experimental setups and applied methodologies (in vivo and in vitro studies) a meta-analysis could not be performed. No ongoing clinical trials with dopaminergic compounds in IBD patients were found. Conclusions: the impairment of the dopaminergic system seems to be a significant, yet underestimated, feature of IBD, and more in-depth observational studies are needed to further support the existing preclinical data.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mitsuaki Kashiwagi ◽  
Mika Kanuka ◽  
Kaeko Tanaka ◽  
Masayo Fujita ◽  
Ayaka Nakai ◽  
...  

AbstractDespite the established roles of the dopaminergic system in promoting arousal, the effects of loss of dopamine on the patterns of sleep and wakefulness remain elusive. Here, we examined the sleep architecture of dopamine-deficient (DD) mice, which were previously developed by global knockout of tyrosine hydroxylase and its specific rescue in noradrenergic and adrenergic neurons. We found that DD mice have reduced time spent in wakefulness. Unexpectedly, DD mice also exhibited a marked reduction in the time spent in rapid eye movement (REM) sleep. The electroencephalogram power spectrum of all vigilance states in DD mice were also affected. These results support the current understanding of the critical roles of the dopaminergic system in maintaining wakefulness and also implicate its previously unknown effects on REM sleep.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Ikezawa ◽  
Fusako Yokochi ◽  
Ryoichi Okiyama ◽  
Satoko Kumada ◽  
Maya Tojima ◽  
...  

Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia.Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT).Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn–Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined.Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area (r = −0.49, p < 0.05) and the cSBR (r = −0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN (p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia (p < 0.5 × 10−6).Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD.


2021 ◽  
Vol 22 (22) ◽  
pp. 12366
Author(s):  
Francesca Chiara Pignalosa ◽  
Antonella Desiderio ◽  
Paola Mirra ◽  
Cecilia Nigro ◽  
Giuseppe Perruolo ◽  
...  

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA’s role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.


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