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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/28714952/a-circuit-based-mechanism-underlying-familiarity-signaling-and-the-preference-for-novelty
#1
Susanna Molas, Rubing Zhao-Shea, Liwang Liu, Steven R DeGroot, Paul D Gardner, Andrew R Tapper
Novelty preference (NP) is an evolutionarily conserved, essential survival mechanism often dysregulated in neuropsychiatric disorders. NP is mediated by a motivational dopamine signal that increases in response to novel stimuli, thereby driving exploration. However, the mechanism by which once-novel stimuli transition to familiar stimuli is unknown. Here we describe a neuroanatomical substrate for familiarity signaling, the interpeduncular nucleus (IPN) of the midbrain, which is activated as novel stimuli become familiar with multiple exposures...
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28714503/protective-effects-of-fisetin-and-other-berry-flavonoids-in-parkinson-s-disease
#2
REVIEW
Pamela Maher
Parkinson's disease (PD) is an age-associated degenerative disease of the midbrain that results from the loss of dopaminergic neurons in the substantia nigra. It initially presents as a movement disorder with cognitive and other behavioral problems appearing later in the progression of the disease. Current therapies for PD only delay the onset or reduce the motor symptoms. There are no treatments to stop the nerve cell death or to cure the disease. It is becoming increasingly clear that neurological diseases such as PD are multi-factorial involving disruptions in multiple cellular systems...
July 17, 2017: Food & Function
https://www.readbyqxmd.com/read/28697798/a-proteomic-analysis-of-lrrk2-binding-partners-reveals-interactions-with-multiple-signaling-components-of-the-wnt-pcp-pathway
#3
Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients...
July 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28696429/glud1-linked-to-schizophrenia-controls-the-burst-firing-of-dopamine-neurons
#4
N Benamer, F Marti, R Lujan, R Hepp, T G Aubier, A A M Dupin, G Frébourg, S Pons, U Maskos, P Faure, Y A Hay, B Lambolez, L Tricoire
Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28672859/astrocytic-expression-of-gsta4-is-associated-to-dopaminergic-neuroprotection-in-a-rat-6-ohda-model-of-parkinson-s-disease
#5
Michael Jewett, Itzia Jimenez-Ferrer, Maria Swanberg
Idiopathic Parkinson's disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD...
June 26, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28655632/normative-data-of-dopaminergic-neurotransmission-functions-in-substantia-nigra-measured-with-mri-and-pet-neuromelanin-dopamine-synthesis-dopamine-transporters-and-dopamine-d2-receptors
#6
Hiroshi Ito, Hiroshi Kawaguchi, Fumitoshi Kodaka, Hiroyuki Takuwa, Yoko Ikoma, Hitoshi Shimada, Yasuyuki Kimura, Chie Seki, Hitoshi Kubo, Shiro Ishii, Harumasa Takano, Tetsuya Suhara
The central dopaminergic system is of major importance in the pathophysiology of Parkinson's disease, schizophrenia, and other neuropsychiatric disorders. In the present study, the normative data of dopaminergic neurotransmission functions in the midbrain, consisting of neuromelanin, dopamine synthesis, dopamine transporters and dopamine D2 receptors, were constructed using magnetic resonance (MR) imaging and positron emission tomography (PET). PET studies with L-[β-(11)C]DOPA, [(18)F]FE-PE2I and [(11)C]FLB457 and MRI studies were performed on healthy young men...
June 26, 2017: NeuroImage
https://www.readbyqxmd.com/read/28650520/immature-midbrain-dopaminergic-neurons-derived-from-floor-plate-method-improve-cell-transplantation-therapy-efficacy-for-parkinson-s-disease
#7
Lifeng Qiu, Mei-Chih Liao, Allen K Chen, Shunhui Wei, Shaoping Xie, Shaul Reuveny, Zhi Dong Zhou, Walter Hunziker, Eng King Tan, Steve K W Oh, Li Zeng
Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplantation in PD therapy. Here, we transplanted three types of mDA cells, DA progenitors (differentiated in vitro for 16 days [D16]), immature DA neurons (D25), and DA neurons (D35), into PD mice and found that all three types of cells showed high viability and strong neuronal differentiation in vivo...
June 26, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#8
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28627418/alterations-in-neuronal-control-of-body-weight-and-anxiety-behavior-by-glutathione-peroxidase-4-deficiency
#9
Sonja C Schriever, Annemarie Zimprich, Katrin Pfuhlmann, Peter Baumann, Florian Giesert, Valentina Klaus, Dhiraj G Kabra, Ulrich Hafen, Artem Romanov, Matthias H Tschöp, Wolfgang Wurst, Marcus Conrad, Sabine M Hölter, Daniela Vogt Weisenhorn, Paul T Pfluger
Elevated levels of oxidative stress and neuronal inflammation in the hypothalamus or ventral midbrain, respectively, represent common denominators for obesity and Parkinson's Disease (PD). However, little is known about defense mechanisms that protect neurons in these regions from oxidative damage. Here, we aimed to assess whether murine Gpx4, a crucial antioxidant enzyme that protects neurons from membrane damage and ferroptosis, is critical for the protection from neuronal inflammation in two distinct pathophysiologic diseases, namely metabolic dysfunction in diet-induced obesity or PD...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28617379/-immunohistochemical-characteristics-of-the-substantia-nigra-neurons-of-the-human
#10
D E Korzhevskii, I P Grigor'ev, E G Sukhorukova, V V Gusel'nikova
AIM: To determine the cytochemical characteristics of unchanged neurons of the human substantia nigra using a wide range of immunocytochemical markers some of which (glutamate decarboxylase-65, PGP 9.5, non-phosphorylated neurofilament proteins, alpa-tubulin) have never been used for study of human dopaminergic neurons. MATERIAL AND METHODS: Fragments of human midbrain (17 men and women, aged from 28 to 78 years) from the archives of the Department of General and Specific Morphology of the Institute of Experimental Medicine were used...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28616718/effect-of-intrastriatal-6-ohda-lesions-on-extrastriatal-brain-structures-in-the-mouse
#11
Birte Becker, Melek Demirbas, Sonja Johann, Adib Zendedel, Cordian Beyer, Hans Clusmann, Stefan Jean-Pierre Haas, Andreas Wree, Sonny Kian Hwie Tan, Markus Kipp
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor and non-motor symptoms. The underlying pathology of non-motor symptoms is poorly understood. Discussed are pathological changes of extrastriatal brain structures. In this study, we characterized histopathological alterations of extrastriatal brain structures in the 6-hydroxydopamine (6-OHDA) PD animal model. Lesions were induced by unilateral stereotactic injections of 6-OHDA into the striatum or medial forebrain bundle of adult male mice...
June 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28602690/dorsal-raphe-dopamine-neurons-modulate-arousal-and-promote-wakefulness-by-salient-stimuli
#12
Jounhong Ryan Cho, Jennifer B Treweek, J Elliott Robinson, Cheng Xiao, Lindsay R Bremner, Alon Greenbaum, Viviana Gradinaru
Ventral midbrain dopamine (DA) is unambiguously involved in motivation and behavioral arousal, yet the contributions of other DA populations to these processes are poorly understood. Here, we demonstrate that the dorsal raphe nucleus DA neurons are critical modulators of behavioral arousal and sleep-wake patterning. Using simultaneous fiber photometry and polysomnography, we observed time-delineated dorsal raphe nucleus dopaminergic (DRN(DA)) activity upon exposure to arousal-evoking salient cues, irrespective of their hedonic valence...
June 7, 2017: Neuron
https://www.readbyqxmd.com/read/28585381/modeling-parkinson-s-disease-with-induced-pluripotent-stem-cells-harboring-%C3%AE-synuclein-mutations
#13
Karamjit Singh Dolt, Fella Hammachi, Tilo Kunath
Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Mutations in genes such as SNCA cause PD in an autosomal dominant manner and patients have motor and non-motor symptoms that are typical for sporadic PD...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28572791/hunger-and-satiety-gauge-reward-sensitivity
#14
REVIEW
Ryan Michael Cassidy, Qingchun Tong
Many of the neurocircuits and hormones known to underlie the sensations of hunger and satiety also substantially alter the activity of the dopaminergic reward system. Much interest lies in the ways that hunger, satiety, and reward tie together, as the epidemic of obesity seems tied to the recent development and mass availability of highly palatable foods. In this review, we will first discuss the basic neurocircuitry of the midbrain and basal forebrain reward system. We will elaborate how several important mediators of hunger-the agouti-related protein neurons of the arcuate nucleus, the lateral hypothalamic nucleus, and ghrelin-enhance the sensitivity of the dopaminergic reward system...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28569794/p7c3-inhibits-gsk3%C3%AE-activation-to-protect-dopaminergic-neurons-against-neurotoxin-induced-cell-death-in-vitro-and-in-vivo
#15
Chao Gu, Yan Zhang, Qingsong Hu, Jiayuan Wu, Haigang Ren, Chun-Feng Liu, Guanghui Wang
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Although its pathogenesis remains unclear, mitochondrial dysfunction plays a vital role in the pathology of PD. P7C3, an aminopropyl carbazole, possesses a significant neuroprotective ability in several neurodegenerative disorders, including PD. Here, we showed that P7C3 stabilized mitochondrial membrane potential, reduced reactive oxygen species production, and inhibited cytochrome c release in MES23.5 cells (a dopaminergic (DA) cell line) exposed to 1-methyl-4-phenylpyridinium (MPP(+))...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28566754/stroke-triggers-nigrostriatal-plasticity-and-increases-alcohol-consumption-in-rats
#16
Cathy C Y Huang, Tengfei Ma, Emily A Roltsch Hellard, Xuehua Wang, Amutha Selvamani, Jiayi Lu, Farida Sohrabji, Jun Wang
Excessive alcohol consumption is a known risk factor for stroke, but the effect of stroke on alcohol intake is unknown. The dorsomedial striatum (DMS) and midbrain areas of the nigrostriatal circuit are critically associated to stroke and alcohol addiction. Here we sought to explore the influence of stroke on alcohol consumption and to uncover the underlying nigrostriatal mechanism. Rats were trained to consume alcohol using a two-bottle choice or operant self-administration procedure. Retrograde beads were infused into the DMS or midbrain to label specific neuronal types, and ischemic stroke was induced in the dorsolateral striatum (DLS)...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28560316/vmat2-mediated-neurotransmission-from-midbrain-leptin-receptor-neurons-in-feeding-regulation
#17
Yuanzhong Xu, Yungang Lu, Pingwen Xu, Leandra R Mangieri, Elsa Isingrini, Yong Xu, Bruno Giros, Qingchun Tong
Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28559307/cortical-neurons-multiplex-reward-related-signals-along-with-sensory-and-motor-information
#18
Arjun Ramakrishnan, Yoon Woo Byun, Kyle Rand, Christian E Pedersen, Mikhail A Lebedev, Miguel A L Nicolelis
Rewards are known to influence neural activity associated with both motor preparation and execution. This influence can be exerted directly upon the primary motor (M1) and somatosensory (S1) cortical areas via the projections from reward-sensitive dopaminergic neurons of the midbrain ventral tegmental areas. However, the neurophysiological manifestation of reward-related signals in M1 and S1 are not well understood. Particularly, it is unclear how the neurons in these cortical areas multiplex their traditional functions related to the control of spatial and temporal characteristics of movements with the representation of rewards...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28552228/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-a-european-approach-stem-pd
#19
Agnete Kirkeby, Malin Parmar, Roger A Barker
The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552226/preparation-characterization-and-banking-of-clinical-grade-cells-for-neural-transplantation-scale-up-fingerprinting-and-genomic-stability-of-stem-cell-lines
#20
Ammar Natalwala, Tilo Kunath
Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles...
2017: Progress in Brain Research
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