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https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#1
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096656/analysis-of-pramipexole-dose-response-relationships-in-parkinson-s-disease
#2
Ying Wang, Sheng-Gang Sun, Sui-Qiang Zhu, Chun-Feng Liu, Yi-Ming Liu, Qing Di, Hui-Fang Shang, Yan Ren, Wei Xiang, Sheng-Di Chen
BACKGROUND: Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson's disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined. METHODS: Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson's Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#3
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina 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 extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#4
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28095073/preclinical-and-potential-applications-of-common-western-herbal-supplements-as-complementary-treatment-in-parkinson-s-disease
#5
Luke A Morgan, Oliver Grundmann
Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system...
January 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28095003/cocaine-addiction-as-a-homeostatic-reinforcement-learning-disorder
#6
Mehdi Keramati, Audrey Durand, Paul Girardeau, Boris Gutkin, Serge H Ahmed
Drug addiction implicates both reward learning and homeostatic regulation mechanisms of the brain. This has stimulated 2 partially successful theoretical perspectives on addiction. Many important aspects of addiction, however, remain to be explained within a single, unified framework that integrates the 2 mechanisms. Building upon a recently developed homeostatic reinforcement learning theory, the authors focus on a key transition stage of addiction that is well modeled in animals, escalation of drug use, and propose a computational theory of cocaine addiction where cocaine reinforces behavior due to its rapid homeostatic corrective effect, whereas its chronic use induces slow and long-lasting changes in homeostatic setpoint...
January 16, 2017: Psychological Review
https://www.readbyqxmd.com/read/28094815/drd2-co-expression-network-and-a-related-polygenic-index-predict-imaging-behavioral-and-clinical-phenotypes-linked-to-schizophrenia
#7
G Pergola, P Di Carlo, E D'Ambrosio, B Gelao, L Fazio, M Papalino, A Monda, G Scozia, B Pietrangelo, M Attrotto, J A Apud, Q Chen, V S Mattay, A Rampino, G Caforio, D R Weinberger, G Blasi, A Bertolino
Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28094812/putative-presynaptic-dopamine-dysregulation-in-schizophrenia-is-supported-by-molecular-evidence-from-post-mortem-human-midbrain
#8
T D Purves-Tyson, S J Owens, D A Rothmond, G M Halliday, K L Double, J Stevens, T McCrossin, C Shannon Weickert
The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28094353/surfactant-free-synthesis-of-three-dimensional-nitrogen-doped-hierarchically-porous-carbon-and-its-application-as-an-electrode-modification-material-for-simultaneous-sensing-of-ascorbic-acid-dopamine-and-uric-acid
#9
Anaclet Nsabimana, Jianping Lai, Suping Li, Pan Hui, Zhongyuan Liu, Guobao Xu
Three-dimensional N-doped hierarchically porous carbon (3D NHPC) was synthesized successfully without using any surfactant or etching agent. This simple and effective synthesis method was accomplished by solvothermal synthesis followed by pyrolysis. The physical morphology and chemical composition of 3D NHPC were verified by scanning electron microscopy, nitrogen adsorption-desorption, and X-ray photoelectron spectroscopy. Its structural studies reveal that it exhibits a micro-mesoporous hierarchical structure and contains C, O and N atoms forming different functional groups...
January 17, 2017: Analyst
https://www.readbyqxmd.com/read/28094018/single-cell-analysis-reveals-a-close-relationship-between-differentiating-dopamine-and-subthalamic-nucleus-neuronal-lineages
#10
Nigel Kee, Nikolaos Volakakis, Agnete Kirkeby, Lina Dahl, Helena Storvall, Sara Nolbrant, Laura Lahti, Åsa K Björklund, Linda Gillberg, Eliza Joodmardi, Rickard Sandberg, Malin Parmar, Thomas Perlmann
Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them...
January 5, 2017: Cell Stem Cell
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
#11
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
https://www.readbyqxmd.com/read/28092083/role-of-dopamine-d2-d3-receptors-in-development-plasticity-and-neuroprotection-in-human-ipsc-derived-midbrain-dopaminergic-neurons
#12
Federica Bono, Paola Savoia, Adele Guglielmi, Massimo Gennarelli, Giovanna Piovani, Sandra Sigala, Damiana Leo, Stefano Espinoza, Raul R Gainetdinov, Paola Devoto, PierFranco Spano, Cristina Missale, Chiara Fiorentini
The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28090181/how-much-we-think-of-ourselves-and-how-little-we-think-of-others-an-investigation-of-the-neuronal-signature-of-self-consciousness-between-different-personality-traits-through-an-event-related-potential-study
#13
Auwal Bello Hassan, Tahamina Begum, Mohammed Faruque Reza, Nasir Yusoff
BACKGROUND: Previous studies have revealed that self-related tasks (items) receive more attention than non-self-related, and that they elicit event-related potential (ERP) components with larger amplitudes. Since personality has been reported as one of the biological correlates influencing these components, as well as our behavioural differences, it is important to examine how it affects our self-consciousness in relation to tasks of varied relevance and the neurological basis. METHODS: A total of 33 male and female undergraduate Malaysian medical students of Universiti Sains Malaysia (USM) participated in the study...
November 2016: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28089852/dopamine-d1-receptor-agonist-treatment-attenuates-extinction-of-morphine-conditioned-place-preference-while-increasing-dendritic-complexity-in-the-nucleus-accumbens-core
#14
Kendra L Kobrin, Danielle T Arena, Stephen C Heinrichs, Olivia H Nguyen, Gary B Kaplan
The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions...
January 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28088727/representativeness-of-clinical-pet-study-participants-with-schizophrenia-a-systematic-review
#15
So Kirino, Takefumi Suzuki, Hiroyoshi Takeuchi, Masaru Mimura, Hiroyuki Uchida
While positron emission tomography (PET) studies have provided invaluable data on antipsychotic effects, selection bias remains a serious concern. A systematic review of PET studies that measured dopamine D2 receptor blockade with antipsychotics was conducted to examine their inclusion/exclusion criteria, using PubMed, EMBASE, and ClinicalTrials.gov (last search, September 2016). PET studies were included if they measured D2 receptor occupancy in patients with schizophrenia and included introduction of antipsychotic treatment or antipsychotic regimen change in a systematic manner...
January 5, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28088578/the-effect-of-long-term-hindlimb-unloading-on-the-expression-of-risk-neurogenes-encoding-elements-of-serotonin-dopaminergic-systems-and-apoptosis-comparison-with-the-effect-of-actual-spaceflight-on-mouse-brain
#16
E A Kulikova, V A Kulikov, N A Sinyakova, A V Kulikov, N K Popova
The study of spaceflight effects on the brain is technically complex concern; complicated by the problem of applying an adequate ground model. The most-widely used experimental model to study the effect of microgravity is the tail-suspension hindlimb unloading model; however, its compliance with the effect of actual spaceflight on the brain is still unclear. We evaluated the effect of one month hindlimb unloading on the expression of genes related to the brain neuroplasticity - brain neutotrophic factors (Gdnf, Cdnf), apoptotic factors (Bcl-xl, Bax), serotonin- and dopaminergic systems (5-HT2A, Maoa, Maob, Th, D1r, Comt), and compared the results with the data obtained on mice that spent one month in spaceflight on Russian biosatellite Bion-M1...
January 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28088492/pikuni-blackfeet-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#17
Aurélie de Rus Jacquet, Mitali Arun Tambe, Sin Ying Ma, George P McCabe, Jay Hansford C Vest, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28088287/insulin-like-growth-factor-binding-protein-3-deficiency-leads-to-behavior-impairment-with-monoaminergic-and-synaptic-dysfunction
#18
Hongmei Dai, Yu-Ichi Goto, Masayuki Itoh
Insulin-like growth factor binding protein (IGFBP)-3 regulates IGF bioactivity, induces apoptosis, and inhibits cell growth independent of IGFs, but the functional role of IGFBP3 in the brain is not clear. In the present study, we revealed the effect of IGFBP3 on the brain by characterizing the phenotype of Igfbp3-null mice. Compared with wild-type mice, Igfbp3-null mice had significantly decreased IGF-1 content in the brain but no change in weights of brain and body. In Igfbp3-null mice, the number of dendritic spines was significantly reduced, and the dendritic diameter was thickening...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28088038/evidence-of-functional-duplicity-of-nestin-expression-in-the-adult-mouse-midbrain
#19
Parisa Farzanehfar, Shi Sheng Lu, Anupa Dey, Dharshani Musiienko, Hamzah Baagil, Malcolm K Horne, Tim D Aumann
Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc) is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD). Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs) in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28087732/novel-gnb1-mutations-disrupt-assembly-and-function-of-g-protein-heterotrimers-and-cause-global-developmental-delay-in-humans
#20
Katja Lohmann, Ikuo Masuho, Dipak N Patil, Hauke Baumann, Eva Hebert, Sofia Steinrücke, Daniel Trujillano, Nickolas K Skamangas, Valerija Dobricic, Irina Hüning, Gabriele Gillessen-Kaesbach, Ana Westenberger, Dusanka Savic-Pavicevic, Alexander Münchau, Gabriela Oprea, Christine Klein, Arndt Rolfs, Kirill A Martemyanov
Global developmental delay (GDD), often accompanied by intellectual disability, seizures and other features is a severe, clinically and genetically highly heterogeneous childhood-onset disorder. In cases where genetic causes have been identified, de-novo mutations in neuronally expressed genes are a common scenario. These mutations can be best identified by exome sequencing of parent-offspring trios. De novo mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) gene, encoding the Gβ1 subunit of heterotrimeric G proteins, have recently been identified as a novel genetic cause of GDD...
January 13, 2017: Human Molecular Genetics
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