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dopamine dysfunction

Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
Paola Imbriani, Tommaso Schirinzi, Maria Meringolo, Nicola B Mercuri, Antonio Pisani
Significant advances have been made in the understanding of the numerous mechanisms involved in Parkinson's disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses...
2018: Frontiers in Neurology
Pablo Garrido-Gil, Antonio Dominguez-Meijide, Rosario Moratalla, Maria J Guerra, Jose L Labandeira-Garcia
Gastrointestinal dysfunction is a common problem in the elderly. Aging-related changes in interactions between local dopaminergic and renin-angiotensin systems (RAS) have been observed in the brain, renal and vascular tissues. However, it is not known if these interactions also occur in the gut, and are dysregulated with aging. We showed a mutual regulation between the colonic dopaminergic system and RAS using young and aged mice deficient for major angiotensin and dopamine receptors. Aged rats showed a marked decrease in colonic dopamine D2 receptor expression, together with an increase in angiotensin type 1 (AT1) receptor expression, a decrease in angiotensin type 2 (AT2) receptor expression (i...
February 16, 2018: Oncotarget
Catherine F Moore, Valentina Sabino, Pietro Cottone
Eating disorders and some forms of obesity are characterized by addictive-like, compulsive eating behavior which contains numerous similarities with compulsive drug use. Food intake is in part mediated by reward and reinforcement processes that can become dysregulated in these disorders. Additionally, impairments in inhibitory control regulation of reward-related responding can cause or further exacerbate binge and compulsive eating. Dysfunctions in two neurotransmitter systems in the mesocorticolimbic pathway, dopamine and glutamate, are thought to contribute to maladaptive eating behaviors...
2018: Frontiers in Pharmacology
Hiep H Tran, Suong N A Dang, Thanh T Nguyen, Anh M Huynh, Linh M Dao, Kaeko Kamei, Masamitsu Yamaguchi, Thao T P Dang
Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Many factors have been shown to contribute to its pathogenesis including genetic and environmental factors. Ubiquitin C-terminal hydrolase L1 (UCHL1) is also known to be involved in the pathogenesis of PD. We herein modeled the study of UCHL1 in Drosophila melanogaster and investigated its functions in PD. The specific knockdown of the Drosophila ortholog of UCHL1 (dUCH) in dopaminergic neurons (DA neurons) led to the underdevelopment and/or degeneration of these neurons, specifically in DL1 DA neuron cluster in the larval brain lobe and PPM2, PPM3, PPL2ab, and VUM DA neuron clusters in the adult brain...
March 13, 2018: Scientific Reports
Michelle W Antoine, Xiaoxia Zhu, Marianne Dieterich, Thomas Brandt, Sarath Vijayakumar, Nicholas McKeehan, Joseph C Arezzo, R Suzanne Zukin, David A Borkholder, Sherri M Jones, Robert D Frisina, Jean M Hébert
How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission...
March 2018: PLoS Biology
Eugenia Tomasella, Lucila Bechelli, Mora Belén Ogando, Camilo Mininni, Mariano N Di Guilmi, Fernanda De Fino, Silvano Zanutto, Ana Belén Elgoyhen, Antonia Marin-Burgin, Diego M Gelman
Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tetsuo Kiso, Ai Moriyama, Masako Furutani, Ritsuko Matsuda, Yukiko Funatsu
Dysfunction of the monoamine systems in the nervous system is associated with the clinical symptoms of fibromyalgia. Reserpine-induced myalgia (RIM) rats are a putative model of fibromyalgia in which muscle pressure thresholds and monoamine content is reduced in the brain and spinal cord. We examined the effects of pregabalin and duloxetine, drugs approved for fibromyalgia treatment, on the levels of extracellular neurotransmitters in the dorsal horn of the spinal cord in RIM rats using microdialysis. Male SD rats were used for all experiments...
March 9, 2018: European Journal of Pharmacology
Luqing Wei, Xiao Hu, Yonggui Yuan, Weiguo Liu, Hong Chen
Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease...
March 9, 2018: Behavioural Brain Research
Devin B Phillips, Craig D Steinback, Sophie É Collins, Desi P Fuhr, Tracey L Bryan, Eric Y L Wong, Vincent Tedjasaputra, Mohit Bhutani, Michael K Stickland
COPD patients have increased central arterial stiffness and muscle sympathetic nervous activity (MSNA), both of which contribute to cardiovascular (CV) dysfunction and increased CV risk. Previous work suggests that COPD patients have elevated carotid chemoreceptor (CC) activity/sensitivity, which may contribute to the elevated MSNA and arterial stiffness. Accordingly, the effect of CC inhibition on central arterial stiffness, MSNA and CV function at rest in COPD patients was examined in a randomized placebo-controlled study...
March 12, 2018: Journal of Physiology
Agostinho Lemos, Rita Meloc, Antonio J Preto, Jose G Almeida, Irina S Moreira, M Natalia D S Cordeiro
Parkinson's Disease (PD) is a long-term neurodegenative brain disorder that mainly affects the motor system. The causes are still unknown, and even though currently there is no cure, several therapeutic options are available to manage its symptoms. The development of novel anti-parkinsonian agents and an understanding of their proper and optimal use are, indeed, highly demanding. For the last decades, L-3,4-DihydrOxyPhenylAlanine or levodopa (L-DOPA) has been the gold-standard therapy for the symptomatic treatment of motor dysfunctions associated to PD...
March 8, 2018: Current Neuropharmacology
Bombi Lee, Insop Shim, Hyejung Lee, Dae-Hyun Hahm
Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure...
March 2018: Korean Journal of Physiology & Pharmacology
Leslie Citrome
Tardive dyskinesia (TD) has long been thought to be a generally irreversible consequence of the use of dopamine receptor blocking agents. There is now an opportunity to successfully manage this condition with agents approved by the US Food and Drug Administration. This is important because TD has not been eliminated with the use of second-generation antipsychotics, and the expansion of antipsychotics to treat conditions other than schizophrenia has resulted in millions of additional individuals at risk for developing TD...
February 28, 2018: Journal of the Neurological Sciences
Jessika C Bridi, Frank Hirth
Parkinson's disease (PD) is characterized by intracellular inclusions of aggregated and misfolded α-Synuclein (α-Syn), and the loss of dopaminergic (DA) neurons in the brain. The resulting motor abnormalities mark the progression of PD, while non-motor symptoms can already be identified during early, prodromal stages of disease. Recent studies provide evidence that during this early prodromal phase, synaptic and axonal abnormalities occur before the degenerative loss of neuronal cell bodies. These early phenotypes can be attributed to synaptic accumulation of toxic α-Syn...
2018: Frontiers in Neuroscience
Sumit Jamwal, Puneet Kumar
Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson's disease and Huntington's disease. Dopamine is important neurotransmitter which play critical role in coordinated body movements. Alteration in level of brain dopamine and receptor radically contribute to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids...
March 1, 2018: Current Neuropharmacology
Moon-Jong Kim, Hong-Seop Kho
Burning mouth syndrome (BMS) is a chronic pain condition characterised by a persistent burning sensation in clinically normal oral mucosa. BMS most commonly occurs in middleaged and elderly women. Various local and systemic factors can cause oral burning symptoms. When all possible local and systemic factors are excluded, burning mouth symptoms can be diagnosed as BMS. Psychophysical tests and histopathological data suggest the involvement of peripheral and central neuropathic mechanisms in BMS etiopathogenesis...
2018: Chinese Journal of Dental Research
Rihua Wang, Xue Zhao, Jin Xu, Yifan Wen, Aiping Li, Ming Lu, Jianwei Zhou
Astrocytic JWA exerts neuroprotective roles by alleviating oxidative stress and inhibiting inflammation. However, the molecular mechanisms of how astrocytic JWA is involved in dopaminergic neurodegeneration in Parkinson's disease (PD) remain largely unknown. In this study, we found that astrocyte-specific JWA knockout mice (JWA CKO) exacerbated dopamine (DA) neuronal loss and motor dysfunction, and reduced the levels of DA and its metabolites in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model...
March 2, 2018: Cell Death & Disease
Matthew J Benskey, Rhyomi C Sellnow, Ivette M Sandoval, Caryl E Sortwell, Jack W Lipton, Fredric P Manfredsson
Human studies and preclinical models of Parkinson's disease implicate the involvement of both the innate and adaptive immune systems in disease progression. Further, pro-inflammatory markers are highly enriched near neurons containing pathological forms of alpha synuclein (α-syn), and α-syn overexpression recapitulates neuroinflammatory changes in models of Parkinson's disease. These data suggest that α-syn may initiate a pathological inflammatory response, however the mechanism by which α-syn initiates neuroinflammation is poorly understood...
2018: Frontiers in Molecular Neuroscience
Chuin Hau Teo, Tomoko Soga, Ishwar S Parhar
Beta-catenin is a protein with dual functions in the cell, playing a role in both adhesion between cells as well as gene transcription via the canonical Wnt signalling pathway. In the canonical Wnt signalling pathway, beta-catenin again plays multiple roles. In the embryonic stage, the regulation of beta-catenin levels activates genes that govern cell proliferation and differentiation. In an adult organism, beta-catenin continues to regulate the cell cycle - as a result over-expression of beta-catenin may lead to cancer...
February 22, 2018: Neuro-Signals
Su Eun Choi, Yun Sun Park, Hyun Chul Koh
Inflammation generated by environmental toxicants including pesticides could be one of the factors underlying neuronal cell damage in neurodegenerative diseases. In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in PC12 cells treated with diquat. We found that diquat induced apoptosis, as demonstrated by the activation of caspases and nuclear condensation, inhibition of mitochondrial complex I activity, and decreased ATP level in PC12 cells. Diquat also reduced the dopamine level, indicating that cell death induced by diquat is due to cytotoxicity of dopaminergic neuronal components in these cells...
February 27, 2018: Environmental Toxicology
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