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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/28808330/generation-and-characterization-of-a-mouse-line-for-monitoring-translation-in-dopaminergic-neurons
#1
Joseph D Dougherty
We developed a mouse line targeting midbrain dopamine neurons for Translating Ribosome Affinity Purification(TRAP). Here, we briefly report on the basic characterization of this mouse line including confirmation of expression of the transgene in midbrain dopamine neurons and validation of its effectiveness in capturing mRNA from these cells. We also report a translational profile of these neurons which may be of use to investigators studying the gene expression of these cells. Finally, we have provided the line to Jackson Laboratories for distribution and use in future studies...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800615/pitx3-and-en1-determine-the-size-and-molecular-programming-of-the-dopaminergic-neuronal-pool
#2
Willemieke M Kouwenhoven, Lars von Oerthel, Marten P Smidt
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28799057/expression-patterns-of-key-sonic-hedgehog-signaling-pathway-components-in-the-developing-and-adult-mouse-midbrain-and-in-the-mn9d-cell-line
#3
Melanie Feuerstein, Enaam Chleilat, Shokoufeh Khakipoor, Konstantinos Michailidis, Christian Ophoven, Eleni Roussa
The temporal dynamic expression of Sonic Hedgehog (SHH) and signaling during early midbrain dopaminergic (mDA) neuron development is one of the key players in establishing mDA progenitor diversity. However, whether SHH signaling is also required during later developmental stages and in mature mDA neurons is less understood. We study the expression of SHH receptors Ptch1 and Gas1 (growth arrest-specific 1) and of the transcription factors Gli1, Gli2 and Gli3 in mouse midbrain during embryonic development [embryonic day (E) 12...
August 11, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28797124/preclinical-development-of-a-vaccine-against-oligomeric-alpha-synuclein-based-on-virus-like-particles
#4
Marika Doucet, Aadil El-Turabi, Franziska Zabel, Benjamin H M Hunn, Nora Bengoa-Vergniory, Milena Cioroch, Mauricio Ramm, Amy M Smith, Ariane Cruz Gomes, Gustavo Cabral de Miranda, Richard Wade-Martins, Martin F Bachmann
Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies...
2017: PloS One
https://www.readbyqxmd.com/read/28781050/direct-midbrain-dopamine-input-to-the-suprachiasmatic-nucleus-accelerates-circadian-entrainment
#5
Ryan M Grippo, Aarti M Purohit, Qi Zhang, Larry S Zweifel, Ali D Güler
Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we identify a novel, direct connection between the DA neurons of the ventral tegmental area (VTA) and the suprachiasmatic nucleus (SCN)...
July 26, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28780783/implications-of-circadian-rhythm-in-dopamine-and-mood-regulation
#6
REVIEW
Jeongah Kim, Sangwon Jang, Han Kyoung Choe, Sooyoung Chung, Gi Hoon Son, Kyungjin Kim
Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28779972/critical-role-of-trpc1-in-thyroid-hormone-dependent-dopaminergic-neuron-development
#7
Chunhai Chen, Qinglong Ma, Ping Deng, Jianjing Yang, Lingling Yang, Min Lin, Zhengping Yu, Zhou Zhou
Thyroid hormones play a crucial role in midbrain dopaminergic (DA) neuron development. However, the underlying molecular mechanisms remain largely unknown. In this study, we revealed that thyroid hormone treatment evokes significant calcium entry through canonical transient receptor potential (TRPC) channels in ventral midbrain neural stem cells and this calcium signaling is essential for thyroid hormone-dependent DA neuronal differentiation. We also found that TRPC1 is the dominant TRPC channel expressed in ventral midbrain neural stem cells which responds to thyroid hormone...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28774789/impaired-cbs-h2s-signaling-axis-contributes-to-mptp-induced-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#8
Yu-Qing Yuan, Ya-Li Wang, Bao-Shi Yuan, Xin Yuan, Xiao-Ou Hou, Jin-Song Bian, Chun-Feng Liu, Li-Fang Hu
Hydrogen sulfide (H2S), a novel neuromodulator, is linked to the pathogenesis of several neurodegenerative disorders. Exogenous application of H2S exerts neuroprotection via anti-inflammation and anti-oxidative stress in animal and cellular models of Parkinson's disease (PD). However, the role of endogenous H2S and the contribution of its various synthases in PD remain unclear. In the present study, we found a decline of plasma and striatal sulfide level in 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model...
August 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28771712/organization-of-alpha-transducin-immunoreactive-system-in-the-brain-and-retina-of-larval-and-young-adult-sea-lamprey-petromyzon-marinus-and-their-relationship-with-other-neural-systems
#9
Antón Barreiro-Iglesias, Blanca Fernández-López, Daniel Sobrido-Cameán, Ramón Anadón
We employed an anti-transducin antibody (Gαt-S), in combination with other markers, to characterize the Gαt-S-immunoreactive (ir) system in the CNS of the sea lamprey, Petromyzon marinus. Gαt-S immunoreactivity was observed in some neuronal populations and numerous fibers distributed throughout the brain. Double Gαt-S- and opsin-ir neurons (putative photoreceptors) are distributed in the hypothalamus (postoptic commissure nucleus, dorsal and ventral hypothalamus) and caudal diencephalon, confirming results of García-Fernández et al...
August 2, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28743955/early-synaptic-dysfunction-induced-by-%C3%AE-synuclein-in-a-rat-model-of-parkinson-s-disease
#10
Jenny-Ann Phan, Kathrine Stokholm, Justyna Zareba-Paslawska, Steen Jakobsen, Kim Vang, Albert Gjedde, Anne M Landau, Marina Romero-Ramos
Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [(11)C]dihydrotetrabenazine (DTBZ)...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28735099/subcellular-expression-of-aquaporin-4-in-substantia-nigra-of-normal-and-mptp-treated-mice
#11
Agnete Prydz, Katja Stahl, Maja Puchades, Nina Davarpaneh, Maria Nadeem, Ole Petter Ottersen, Vidar Gundersen, Mahmood Amiry-Moghaddam
Aquaporin-4 (AQP4) is the predominant water channel in mammalian CNS where it is localized at the perivascular astrocytic foot processes abutting brain microvessels. Several lines of evidence suggest that AQP4 is involved in important homeostatic functions and that mislocalization of the perivascular pool of AQP4 is implicated in several different brain disorders. A recent study suggests that the differential susceptibility of midbrain dopaminergic neurons to the parkinsonogenic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) depends on the expression of AQP4...
July 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28729666/expansion-of-human-midbrain-floor-plate-progenitors-from-induced-pluripotent-stem-cells-increases-dopaminergic-neuron-differentiation-potential
#12
Stefania Fedele, Ginetta Collo, Katharina Behr, Josef Bischofberger, Stephan Müller, Tilo Kunath, Klaus Christensen, Anna Lisa Gündner, Martin Graf, Ravi Jagasia, Verdon Taylor
Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#13
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28725655/cell-replacement-therapy-is-the-remedial-solution-for-treating-parkinson-s-disease
#14
REVIEW
Venkatesan Dhivya, Vellingiri Balachandar
The selective degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) has made an idol target for cell replacement therapies and other emerging surgical treatments. Certainly, by transplantation method, the therapeutic regimens such as human fetal ventral midbrain (hfVM) cells, human embryonic stem cells (hESCs), human neural stem/precursor/ progenitor cells (hNSCs/hNPCs), human mesenchymal stem cells (hMSCs), human induced neural stem cells (hiNSCs), and human induced pluripotent stem cells (hiPSCs) have been used into DA deficient striatum...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28722508/atg5-and-atg7-dependent-autophagy-in-dopaminergic-neurons-regulates-cellular-and-behavioral-responses-to-morphine
#15
Ling-Yan Su, Rongcan Luo, Qianjin Liu, Jing-Ran Su, Lu-Xiu Yang, Yu-Qiang Ding, Lin Xu, Yong-Gang Yao
The molecular basis of chronic morphine exposure remains unknown. In this study, we hypothesized that macroautophagy/autophagy of dopaminergic neurons would mediate the alterations of neuronal dendritic morphology and behavioral responses induced by morphine. Chronic morphine exposure caused Atg5 (autophagy related 5)- and Atg7 (autophagy related 7)-dependent and dopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors. In cultured primary midbrain neurons, morphine treatment significantly reduced total dendritic length and complexity, and this effect could be reversed by knockdown of Atg5 or Atg7...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28720718/phosphorylation-of-amyloid-precursor-protein-by-mutant-lrrk2-promotes-aicd-activity-and-neurotoxicity-in-parkinson-s-disease
#16
Zhong-Can Chen, Wei Zhang, Ling-Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jian-He Peng, Zhi-Dong Zhou, Kah-Leong Lim, Li Zeng, Eng-King Tan
Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28714952/a-circuit-based-mechanism-underlying-familiarity-signaling-and-the-preference-for-novelty
#17
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
#18
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
#19
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
#20
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
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