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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/28214539/lumbee-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#1
Aurélie de Rus Jacquet, Michael Timmers, Sin Ying Ma, Andrew Thieme, George P McCabe, Jay Hansford C Vest, Mary Ann Lila, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD...
February 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28208711/antidepressant-effects-of-aripiprazole-augmentation-for-cilostazol-treated-mice-exposed-to-chronic-mild-stress-after-ischemic-stroke
#2
Yu Ri Kim, Ha Neui Kim, Ki Whan Hong, Hwa Kyoung Shin, Byung Tae Choi
The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202786/dopamine-modulates-adaptive-prediction-error-coding-in-the-human-midbrain-and-striatum
#3
Kelly M J Diederen, Hisham Ziauddeen, Martin D Vestergaard, Tom Spencer, Wolfram Schultz, Paul C Fletcher
Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride)...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28194005/genetic-inhibition-of-neurotransmission-reveals-role-of-glutamatergic-input-to-dopamine-neurons-in-high-effort-behavior
#4
M A Hutchison, X Gu, M F Adrover, M R Lee, T S Hnasko, V A Alvarez, W Lu
Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28191758/preclinical-analysis-of-fetal-human-mesencephalic-neural-progenitor-cell-lines-characterization-and-safety-in-vitro-and-in-vivo
#5
Jisook Moon, Sigrid C Schwarz, Hyun-Seob Lee, Jun Mo Kang, Young-Eun Lee, Bona Kim, Mi-Young Sung, Günter Höglinger, Florian Wegner, Jin Su Kim, Hyung-Min Chung, Sung Woon Chang, Kwang Yul Cha, Kwang-Soo Kim, Johannes Schwarz
We have developed a good manufacturing practice for long-term cultivation of fetal human midbrain-derived neural progenitor cells. The generation of human dopaminergic neurons may serve as a tool of either restorative cell therapies or cellular models, particularly as a reference for phenotyping region-specific human neural stem cell lines such as human embryonic stem cells and human inducible pluripotent stem cells. We cultivated 3 different midbrain neural progenitor lines at 10, 12, and 14 weeks of gestation for more than a year and characterized them in great detail, as well as in comparison with Lund mesencephalic cells...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#6
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells...
February 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28182766/cd24-expression-does-not-affect-dopamine-neuronal-survival-in-a-mouse-model-of-parkinson-s-disease
#7
Simon R W Stott, Shaista Hayat, Tom Carnwath, Shaady Garas, Jonathan P Sleeman, Roger A Barker
Parkinson's disease (PD) is a progressive neurodegenerative condition that is characterised by the loss of specific populations of neurons in the brain. The mechanisms underlying this selective cell death are unknown but by using laser capture microdissection, the glycoprotein, CD24 has been identified as a potential marker of the populations of cells that are affected in PD. Using in situ hybridization and immunohistochemistry on sections of mouse brain, we confirmed that CD24 is robustly expressed by many of these subsets of cells...
2017: PloS One
https://www.readbyqxmd.com/read/28177164/midbrain-dopaminergic-neuron-activity-across-alternating-brain-states-of-urethane-anaesthetised-rat
#8
Magdalena Walczak, Tomasz Błasiak
Midbrain dopaminergic neurons are implicated in the control of motor functions and reward-driven behaviours. The function of this neuronal population is strongly connected with distinct patterns of firing - irregular or bursting, which either maintains basal levels of dopamine or leads to phasic release, respectively. Heterogeneity of dopaminergic neurons, observed on both structural and functional levels, is also reflected in different responses of DA neurons to changes in global brain states. Preparation of urethane anaesthetised animal is a broadly used model to study brain state dependent activity of neurons...
February 8, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28174244/a-novel-floor-plate-boundary-defined-by-adjacent-en1-and-dbx1-microdomains-distinguishes-midbrain-dopamine-and-hypothalamic-neurons
#9
Navid Nouri, Rajeshwar Awatramani
The mesodiencephalic floor plate (mdFP) is the source of diverse neuron types. Yet, how this structure is compartmentalized has not been clearly elucidated. Here, we identify a novel boundary subdividing the mdFP into two microdomains, defined by Engrailed 1 (En1) and developing brain homeobox 1 (Dbx1) Utilizing simultaneous dual and intersectional fate mapping, we demonstrate that this boundary is precisely formed with minimal overlap between En1 and Dbx1 microdomains, unlike many other boundaries. We show that the En1 microdomain gives rise to dopaminergic (DA) neurons, while the Dbx1 microdomain gives rise to subthalamic (STN), premammillary (PM), and posterior hypothalamic (PH) populations...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28170429/cholesterol-contributes-to-dopamine-neuronal-loss-in-mptp-mouse-model-of-parkinson-s-disease-involvement-of-mitochondrial-dysfunctions-and-oxidative-stress
#10
Rajib Paul, Amarendranath Choudhury, Sanjeev Kumar, Anirudha Giri, Rajat Sandhir, Anupom Borah
Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents...
2017: PloS One
https://www.readbyqxmd.com/read/28131726/transplantation-site-influences-the-phenotypic-differentiation-of-dopamine-neurons-in-ventral-mesencephalic-grafts-in-parkinsonian-rats
#11
Marija Fjodorova, Eduardo M Torres, Stephen B Dunnett
Foetal midbrain progenitors have been shown to survive, give rise to different classes of dopamine neurons and integrate into the host brain alleviating Parkinsonian symptoms following transplantation in patients and animal models of the disease. Dopamine neuron subpopulations in the midbrain, namely A9 and A10, can be identified anatomically based on cell morphology and ascending axonal projections. G protein-gated inwardly rectifying potassium channel Girk2 and the calcium binding protein Calbindin are the two best available histochemical markers currently used to label (with some overlap) A9- and A10-like dopamine neuron subtypes, respectively, in tyrosine hydroxylase expressing neurons both in the midbrain and grafts...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28130357/survival-of-a-novel-subset-of-midbrain-dopaminergic-neurons-projecting-to-the-lateral-septum-is-dependent-on-neurod-proteins
#12
Shabana Khan, Simon Stott, Audrey Chabrat, Anna M Truckenbrodt, Bradley Spencer-Dene, Klaus-Armin Nave, François Guillemot, Martin Levesque, Siew-Lan Ang
: Midbrain dopaminergic neurons are highly heterogeneous. They differ in their connectivity and firing patterns, and therefore in their functional properties. The molecular underpinnings of this heterogeneity are largely unknown and there is a paucity of markers that distinguish these functional subsets. In this paper, we report the identification and characterisation of a novel subset of midbrain dopaminergic neurons located in the ventral tegmental area that expresses the basic helix-loop-helix transcription factor, Neurogenic Differentiation Factor-6 (NEUROD6)...
January 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28127418/tualang-honey-protects-the-rat-midbrain-and-lung-against-repeated-paraquat-exposure
#13
Suk Peng Tang, Sirajudeen Kuttulebbai Nainamohamed Salam, Hasnan Jaafar, Siew Hua Gan, Mustapha Muzaimi, Siti Amrah Sulaiman
Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28123558/neuroprotective-effect-of-matrine-on-mptp-induced-parkinson-s-disease-and-on-nrf2-expression
#14
Fanhua Meng, Jianhui Wang, Fuxiang Ding, Yunliang Xie, Yingjie Zhang, Jie Zhu
The incidence rate of Parkinson's disease (PD) is ≤2% in Chinese individuals >65 years old, accounting for 40% of the global total of PD patients. The pathogenesis of PD is not yet clear, and oxidative stress-induced mitochondrial dysfunction is considered to be the main reason for the onset of PD. Studies have shown that matrine exhibits good antioxidant activity. Thus, the present study aimed to observe the protective effect and mechanism of matrine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuron damage...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28121982/activin-a-inhibits-mptp-and-lps-induced-increases-in-inflammatory-cell-populations-and-loss-of-dopamine-neurons-in-the-mouse-midbrain-in-vivo
#15
Sandy Stayte, Peggy Rentsch, Anna R Tröscher, Maximilian Bamberger, Kong M Li, Bryce Vissel
Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28117752/therapeutic-potential-of-induced-neural-stem-cells-for-parkinson-s-disease
#16
Dong-Hee Choi, Ji-Hye Kim, Sung Min Kim, Kyuree Kang, Dong Wook Han, Jongmin Lee
Parkinson's disease (PD) is a chronic, neurodegenerative disorder that results from the loss of cells in the substantia nigra (SN) which is located in the midbrain. However, no cure is available for PD. Recently, fibroblasts have been directly converted into induced neural stem cells (iNSCs) via the forced expression of specific transcription factors. Therapeutic potential of iNSC in PD has not been investigated yet. Here, we show that iNSCs directly converted from mouse fibroblasts enhanced functional recovery in an animal model of PD...
January 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28110217/induced-dopaminergic-neurons-a-new-promise-for-parkinson-s-disease
#17
Zhimin Xu, Xingkun Chu, Houbo Jiang, Haley Schilling, Shengdi Chen, Jian Feng
Motor symptoms that define Parkinson's disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells...
January 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28103901/pathogenic-lrrk2-variants-are-gain-of-function-mutations-that-enhance-lrrk2-mediated-repression-of-%C3%AE-catenin-signaling
#18
Daniel C Berwick, Behzad Javaheri, Andrea Wetzel, Mark Hopkinson, Jonathon Nixon-Abell, Simone Grannò, Andrew A Pitsillides, Kirsten Harvey
BACKGROUND: LRRK2 mutations and risk variants increase susceptibility to inherited and idiopathic Parkinson's disease, while recent studies have identified potential protective variants. This, and the fact that LRRK2 mutation carriers develop symptoms and brain pathology almost indistinguishable from idiopathic Parkinson's disease, has led to enormous interest in this protein. LRRK2 has been implicated in a range of cellular events, but key among them is canonical Wnt signalling, which results in increased levels of transcriptionally active β-catenin...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#19
Jaakko J Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina L Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction and Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in various disorders with disturbed dopamine homeostasis. However, the outcomes from preclinical and clinical studies vary, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28094017/predictive-markers-guide-differentiation-to-improve-graft-outcome-in-clinical-translation-of-hesc-based-therapy-for-parkinson-s-disease
#20
Agnete Kirkeby, Sara Nolbrant, Katarina Tiklova, Andreas Heuer, Nigel Kee, Tiago Cardoso, Daniella Rylander Ottosson, Mariah J Lelos, Pedro Rifes, Stephen B Dunnett, Shane Grealish, Thomas Perlmann, Malin Parmar
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson's disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors...
January 5, 2017: Cell Stem Cell
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