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Dopamine neurons

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https://www.readbyqxmd.com/read/29349573/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-elevates-stimulus-evoked-release-of-dopamine-in-freely-moving-rats
#1
Juho-Matti Renko, Susanne Bäck, Merja H Voutilainen, T Petteri Piepponen, Ilkka Reenilä, Mart Saarma, Raimo K Tuominen
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson's disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348323/epothilone-b-benefits-nigrostriatal-pathway-recovery-by-promoting-microtubule-stabilization-after-intracerebral-hemorrhage
#2
Yang Yang, Xuan Zhang, Hongfei Ge, Wei Liu, Eryi Sun, Yuanyuan Ma, Hengli Zhao, Rongwei Li, Weixiang Chen, Jichao Yuan, Qianwei Chen, Yujie Chen, Xin Liu, John H Zhang, Rong Hu, Xiaotang Fan, Hua Feng
BACKGROUND: Many previous clinical studies have demonstrated that the nigrostriatal pathway, which plays a vital role in movement adjustment, is significantly impaired after stroke, according to medical imaging and autopsies. However, the basic pathomorphological changes have been poorly investigated to date. This study was designed to explore the pathomorphological changes, mechanism, and therapeutic method of nigrostriatal impairment after intracerebral hemorrhage (ICH). METHODS AND RESULTS: Intrastriatal injection of autologous blood or microtubule depolymerization reagent nocodazole was performed to mimic the pathology of ICH in C57/BL6 mice...
January 18, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29344870/cell-specific-rna-quantification-in-human-sn-da-neurons-from-heterogeneous-post-mortem-midbrain-samples-by-uv-laser-microdissection-and-rt-qpcr
#3
Johanna Duda, Michael Fauler, Jan Gründemann, Birgit Liss
Cell specificity of gene expression analysis is from particular relevance when the abundance of target cells is not homogeneous in the compared tissue samples, like it is the case, e.g., when comparing brain tissues from controls and in neurodegenerative disease states. While single-cell gene expression profiling is already a methodological challenge per se, it becomes even more prone to artifacts when analyzing individual cells from human post-mortem samples. Not only because human samples can never be matched as precisely as those from animal models, but also, because the RNA-quality that can be obtained from human samples usually displays a high range of variability...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344679/distribution-and-dynamic-expression-of-serotonin-and-dopamine-in-the-nervous-system-and-ovary-of-holothuria-scabra-during-ovarian-maturation
#4
Arada Chaiyamoon, Ruchanok Tinikul, Supakant Chaichotranunt, Tanes Poomthong, Worawit Suphamungmee, Prasert Sobhon, Yotsawan Tinikul
In the present study, the distribution and dynamic expression of serotonin and dopamine in the nervous system and ovary of the sea cucumber, Holothuria scabra, during different ovarian stages were investigated. We found that serotonin-immunoreactivity was more intense in the neurons and neuropils of the outer ectoneural part, the inner hyponeural part, and the wall of hyponeural canal of radial nerve cord during the mature stages of ovarian cycle, whereas dopamine-immunoreactivity was detected at a higher intensity in these tissues during the early stages...
January 18, 2018: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29339486/cell-type-specific-role-for-nucleus-accumbens-neuroligin-2-in-depression-and-stress-susceptibility
#5
Mitra Heshmati, Hossein Aleyasin, Caroline Menard, Daniel J Christoffel, Meghan E Flanigan, Madeline L Pfau, Georgia E Hodes, Ashley E Lepack, Lucy K Bicks, Aki Takahashi, Ramesh Chandra, Gustavo Turecki, Mary Kay Lobo, Ian Maze, Sam A Golden, Scott J Russo
Behavioral coping strategies are critical for active resilience to stress and depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell adhesion proteins that are constituents of the excitatory and inhibitory synapse. Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates underlying the development of neuropsychiatric disorders with social disturbances such as autism, but the role of NLGN-2 in neuropsychiatric disease states is unclear...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339319/treatment-with-the-noradrenaline-re-uptake-inhibitor-atomoxetine-alone-and-in-combination-with-the-%C3%AE-2-adrenoceptor-antagonist-idazoxan-attenuates-loss-of-dopamine-and-associated-motor-deficits-in-the-lps-inflammatory-rat-model-of-parkinson-s-disease
#6
Justin D Yssel, Eoin O'Neill, Yvonne M Nolan, Thomas J Connor, Andrew Harkin
The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment with atomoxetine and idazoxan, a combination which serves to enhance the extra-synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects following delivery of an inflammatory stimulus, the bacterial endotoxin, lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss were rescued to varying degrees depending on the treatment...
January 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29339293/methylphenidate-significantly-alters-the-functional-coupling-between-the-prefrontal-cortex-and-dopamine-neurons-in-the-ventral-tegmental-area
#7
Ike C Dela Peña, Guofang Shen, Wei-Xing Shi
Amphetamine-like psychostimulants, including methylphenidate, have been shown to produce two opposing effects on dopamine (DA) neurons: a DA receptor-mediated feedback inhibition and a non-DA receptor-mediated excitation. To test whether the latter effect is mediated through the prefrontal cortex (PFC), we made dual-site recordings from the PFC and ventral tegmental area (VTA). Consistent with previous reports, methylphenidate inhibited VTA DA neurons. The D2 receptor antagonist raclopride completely reversed the inhibition and further increased the activity, particularly bursting, to above pre-drug baseline...
January 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29339106/safinamide-a-new-hope-for-parkinson-s-disease
#8
REVIEW
Fábio G Teixeira, Miguel F Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J Salgado
The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death...
January 12, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29339103/comparative-review-of-adult-midbrain-and-striatum-neurogenesis-with-classical-neurogenesis
#9
REVIEW
Parisa Farzanehfar
Parkinson's Disease (PD) motor symptoms are caused by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine cell replacement therapy (DA CRT), either by cell transplantation or endogenous repair, has been a potential treatment to replace dead cells and improve PD motor symptoms. Adult midbrain and striatum have been studied for many years to find evidence of neurogenesis. Although the literature is controversial, recent research has revived the possibility of neurogenesis here...
January 12, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29339089/concentration-gradient-of-noradrenaline-from-the-periphery-to-the-centre-of-the-cornea-a-clue-to-its-origin
#10
Luis Figueira, Carla Ferreira, Catarina Janeiro, Paula Serrao, Fernando Falcao-Reis, Daniel Moura
We set out to demonstrate that the major source of corneal catecholamines is its neuronal release from intrinsic sympathetic nerves rather than circulating or non-neuronal local production. Three concentric segments (central, intermediate, peripheral) were obtained by double trephination (9.5-7.25 mm) performed on corneas harvested from 3-4 month old rabbits and human corneas rejected for transplantation, along with aqueous humour, full iris tissue and blood samples. Endogenous catecholamines were quantified by high pressure liquid chromatography with electrochemical detection (HPLC-ED), and comparison with the uptake of radio-labelled noradrenaline (3H-NA) before and after incubation with cocaine was performed...
January 12, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29337309/role-for-vglut2-in-selective-vulnerability-of-midbrain-dopamine-neurons
#11
Thomas Steinkellner, Vivien Zell, Zachary J Farino, Mark S Sonders, Michael Villeneuve, Robin J Freyberg, Serge Przedborski, Wei Lu, Zachary Freyberg, Thomas S Hnasko
Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29335072/rebound-excitability-mediates-motor-abnormalities-in-parkinson-s-disease
#12
Jeongjin Kim, Daesoo Kim
Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition...
January 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#13
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29332269/behavioral-biochemical-and-molecular-characterization-of-a-parkinson-s-disease-mouse-model-using-the-neurotoxin-2-ch3-mptp-a-novel-approach
#14
Alice Laschuk Herlinger, Agihane Rodrigues Almeida, Sarah Martins Presti-Silva, Evaldo Vitor Pereira, Filipe Andrich, Rita Gomes Wanderley Pires, Cristina Martins-Silva
The neurotoxin MPTP has long been used to create a mouse model of Parkinson's disease (PD). Indeed, several MPTP analogues have been developed, including 2'-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3-MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated...
January 13, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29331395/tyrosine-hydroxylase-as-a-sentinel-for-central-and-peripheral-tissue-responses-in-parkinson-s-progression-evidence-from-clinical-studies-and-neurotoxin-models
#15
REVIEW
M E Johnson, M F Salvatore, S A Maiolo, L Bobrovskaya
Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient's quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role...
January 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29331265/mechanisms-of-memory-disruption-in-depression
#16
REVIEW
Daniel G Dillon, Diego A Pizzagalli
Depressed individuals typically show poor memory for positive events, potentiated memory for negative events, and impaired recollection. These phenomena are clinically important but poorly understood. Compelling links between stress and depression suggest promising candidate mechanisms. Stress can suppress hippocampal neurogenesis, inhibit dopamine neurons, and sensitize the amygdala. We argue that these phenomena may impair pattern separation, disrupt the encoding of positive experiences, and bias retrieval toward negative events, respectively, thus recapitulating core aspects of memory disruption in depression...
January 10, 2018: Trends in Neurosciences
https://www.readbyqxmd.com/read/29331172/blood-phenylalanine-reduction-corrects-cns-dopamine-and-serotonin-deficiencies-and-partially-improves-behavioral-performance-in-adult-phenylketonuric-mice
#17
Shelley R Winn, Tanja Scherer, Beat Thöny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, Cary O Harding
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29330884/synapsin-iii-is-a-key-component-of-%C3%AE-synuclein-fibrils-in-lewy-bodies-of-pd-brains
#18
Francesca Longhena, Gaia Faustini, Tatiana Varanita, Michela Zaltieri, Vanessa Porrini, Isabella Tessari, Pietro Luigi Poliani, Cristina Missale, Barbara Borroni, Alessandro Padovani, Luigi Bubacco, Marina Pizzi, PierFranco Spano, Arianna Bellucci
Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III...
January 13, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29330488/motor-skill-learning-and-reward-consumption-differentially-affect-vta-activation
#19
Susan Leemburg, Tara Canonica, Andreas Luft
Dopamine release from the ventral tegmental area (VTA) terminals in the primary motor cortex (M1) enables motor skill acquisition. Here, we test the hypothesis that dopaminergic VTA neurons projecting to M1 are activated when rewards are obtained during motor skill acquisition, but not during task execution at plateau performance, or by rewards obtained without performing skilled movements. Rats were trained to perform a skilled reaching task for 3 days (acquisition) or 7 days (plateau). In combination with retrograde labelling of VTA-to-M1 projection neurons, double immunofluorescence for c-fos and tyrosine hydroxylase (TH) was used to assess activation of dopaminergic and non-dopaminergic VTA neurons...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329382/adolescent-synthetic-cannabinoid-exposure-produces-enduring-changes-in-dopamine-neuron-activity-in-a-rodent-model-of-schizophrenia-susceptibility
#20
David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Background: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. Method: We have recently developed a novel rodent model of schizophrenia susceptibility, the F2 MAM rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype...
January 10, 2018: International Journal of Neuropsychopharmacology
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