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Dopaminergic neuron

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https://www.readbyqxmd.com/read/27913104/d-ala2-gip-glu-pal-is-neuroprotective-in-a-chronic-parkinson-s-disease-mouse-model-and-increases-bndf-expression-while-reducing-neuroinflammation-and-lipid-peroxidation
#1
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Parkinson's disease (PD). Therefore, treatment to improve insulin resistance in T2DM may be useful for PD patients. Glucose dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family that can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. We had shown previously that D-Ala2-GIP-glu-PAL, a novel long-acting GIP analogue, can play a neuroprotective role in the PD mouse model induced by acute MPTP injection...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27911941/copper-oxide-nanoparticles-impact-several-toxicological-endpoints-and-cause-neurodegeneration-in-caenorhabditis-elegans
#2
Michael J Mashock, Tyler Zanon, Anthony D Kappell, Lisa N Petrella, Erik C Andersen, Krassimira R Hristova
Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C...
2016: PloS One
https://www.readbyqxmd.com/read/27909152/involvement-of-mesolimbic-dopaminergic-network-in-neuropathic-pain-relief-by-treadmill-exercise-a-study-for-specific-neural-control-with-gi-dreadd-in-mice
#3
Kenta Wakaizumi, Takashige Kondo, Yusuke Hamada, Michiko Narita, Rui Kawabe, Hiroki Narita, Moe Watanabe, Shigeki Kato, Emiko Senba, Kazuto Kobayashi, Naoko Kuzumaki, Akihiro Yamanaka, Hiroshi Morisaki, Minoru Narita
BACKGROUND: Exercise alleviates pain and it is a central component of treatment strategy for chronic pain in clinical setting. However, little is known about mechanism of this exercise-induced hypoalgesia. The mesolimbic dopaminergic network plays a role in positive emotions to rewards including motivation and pleasure. Pain negatively modulates these emotions, but appropriate exercise is considered to activate the dopaminergic network. We investigated possible involvement of this network as a mechanism of exercise-induced hypoalgesia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27908749/a-new-role-for-gabaergic-transmission-in-the-control-of-male-rat-sexual-behavior-expression
#4
Gabriela Rodríguez-Manzo, Ana Canseco-Alba
GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABAA receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state...
November 28, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27904494/anti-apoptotic-effect-of-shudipingchan-granule-in-the-substantia-nigra-of-rat-models-of-parkinson-s-disease
#5
Qing Ye, Xiao-Lei Yuan, Jing He, Jie Zhou, Can-Xing Yuan, Xu-Ming Yang
Levodopa is the gold-standard treatment for Parkinson's disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the effect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson's disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily) with or without Shudipingchan granule (7...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903866/nigral-dopaminergic-pak4-prevents-neurodegeneration-in-rat-models-of-parkinson-s-disease
#6
So-Yoon Won, Mee-Hee Park, Soon-Tae You, Seung-Won Choi, Hyong-Kyu Kim, Catriona McLean, Suk-Chul Bae, Sang Ryong Kim, Byung Kwan Jin, Kun Ho Lee, Eun-Young Shin, Eung-Gook Kim
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. No neuroprotective treatments have successfully prevented the progression of this disease. We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons. We observed PAK4 immunoreactivity in rat and human DA neurons in brain tissue, but not in microglia or astrocytes. PAK4 activity was markedly decreased in postmortem brain tissue from PD patients and in rodent models of PD...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903732/parkin-deficiency-reduces-hippocampal-glutamatergic-neurotransmission-by-impairing-ampa-receptor-endocytosis
#7
Giuseppe P Cortese, Mei Zhu, Damian Williams, Sarah Heath, Clarissa L Waites
: Mutations in the gene encoding Parkin, an E3 ubiquitin ligase, lead to juvenile-onset Parkinson's disease by inducing the selective death of midbrain dopaminergic neurons. Accumulating evidence indicates that Parkin also has an important role in excitatory glutamatergic neurotransmission, although its precise mechanism of action remains unclear. Here, we investigate Parkin's role at glutamatergic synapses of rat hippocampal neurons. We find that Parkin-deficient neurons exhibit significantly reduced AMPA receptor (AMPAR)-mediated currents and cell-surface expression, and that these phenotypes result from decreased postsynaptic expression of the adaptor protein Homer1, which is necessary for coupling AMPAR endocytic zones with the postsynaptic density...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27902767/towards-a-non-human-primate-model-of-alpha-synucleinopathy-for-development-of-therapeutics-for-parkinson-s-disease-optimization-of-aav1-2-delivery-parameters-to-drive-sustained-expression-of-alpha-synuclein-and-dopaminergic-degeneration-in-macaque
#8
James B Koprich, Tom H Johnston, Gabriela Reyes, Vanessa Omana, Jonathan M Brotchie
Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27900791/robust-graft-survival-and-normalized-dopaminergic-innervation-does-not-obligate-recovery-in-a-pd-patient
#9
Jeffrey H Kordower, Christopher G Goetz, Yaping Chu, Glenda M Halliday, Daniel A Nicholson, Timothy Musial, David J Marmion, A Jon Stoessl, Vesna Sossi, Thomas B Freeman, C Warren Olanow
OBJECTIVE: The main goal of dopamine cell replacement therapy in Parkinson's disease (PD) is to provide clinical benefit mediated by graft survival with nigrostriatal reinnervation. We report a dichotomy between graft structure and clinical function in a patient dying sixteen years following fetal nigral grafting. METHODS: A 55-year-old levodopa-responsive woman with PD received bilateral putamenal fetal mesencephalic grafts as part of an NIH-sponsored double-blind sham-controlled trial...
November 30, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27900485/serum-glutathione-peroxidase-xanthine-oxidase-and-superoxide-dismutase-activities-and-malondialdehyde-levels-in-patients-with-parkinson-s-disease
#10
Burcu Gökçe Çokal, Mustafa Yurtdaş, Selda Keskin Güler, Hafize Nalan Güneş, Ceyla Ataç Uçar, Bilal Aytaç, Zahide Esra Durak, Tahir Kurtuluş Yoldaş, İlker Durak, Hikmet Can Çubukçu
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Oxidative stress has been hypothesized to play a major role in the development of PD in various studies. This study assessed to investigate oxidative and anti-oxidative status in PD patients. We evaluated oxidant/antioxidant status by measuring serum malondialdehyde (MDA) levels, xanthine oxidase (XO) activities, and activities of antioxidant enzymes, namely, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)...
November 30, 2016: Neurological Sciences
https://www.readbyqxmd.com/read/27899629/enhanced-non-viral-gene-delivery-by-coordinated-endosomal-release-and-inhibition-of-%C3%AE-tubulin-deactylase
#11
Yoon Khei Ho, Li Han Zhou, Kam C Tam, Heng Phon Too
Efficient non-viral gene delivery is highly desirable but often unattainable with some cell-types. We report here that non-viral DNA polyplexes can efficiently transfect differentiated neuronal and stem cells. Polyplex transfection centrifugation protocols was enhanced by including a simultaneous treatment with a DOPE/CHEMS lipid suspension and a microtubule inhibitor, Tubastatin A. Lipoplex transfection protocols were not improved by this treatment. This mechanism of action was unravelled by systematically identifying and rationally mitigating barriers limiting high transfection efficiency, allowing unexpected improvements in the transfection of mesenchymal stem cells (MSC), primary neuron and several hard-to-transfect cell types beyond what are currently achievable using cationic polymers...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899296/targeting-the-norepinephrinergic-system-in-parkinson-s-disease-and-related-disorders-the-locus-coeruleus-story
#12
Yannick Vermeiren, Peter P De Deyn
Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are related, progressive and debilitating neurodegenerative disorders with hallmark features that include a variety of motor and non-motor symptoms (behavioral, autonomic and cognitive dysfunction). For almost half a century, the motor aspects have been attributed to Lewy pathology (LP) predominantly in the substantia nigra (SN), causing a major loss of dopaminergic neurons. However, the relative success of dopaminergic replacement therapies for alleviation of solely the parkinsonian features has prompted researchers to further explore other monoaminergic strategies which may tackle all PD-related aspects...
November 26, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27895562/brain-computation-is-organized-via-power-of-two-based-permutation-logic
#13
Kun Xie, Grace E Fox, Jun Liu, Cheng Lyu, Jason C Lee, Hui Kuang, Stephanie Jacobs, Meng Li, Tianming Liu, Sen Song, Joe Z Tsien
There is considerable scientific interest in understanding how cell assemblies-the long-presumed computational motif-are organized so that the brain can generate intelligent cognition and flexible behavior. The Theory of Connectivity proposes that the origin of intelligence is rooted in a power-of-two-based permutation logic (N = 2 (i) -1), producing specific-to-general cell-assembly architecture capable of generating specific perceptions and memories, as well as generalized knowledge and flexible actions. We show that this power-of-two-based permutation logic is widely used in cortical and subcortical circuits across animal species and is conserved for the processing of a variety of cognitive modalities including appetitive, emotional and social information...
2016: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/27894919/resveratrol-attenuates-mpp-induced-mitochondrial-dysfunction-and-cell-apoptosis-via-akt-gsk-3%C3%AE-pathway-in-sn4741-cells
#14
Weijun Zeng, Wei Zhang, Fangfang Lu, Li Gao, Guodong Gao
Oxidative stress and mitochondrial dysfunction play crucial role in the dopaminergic neurons death, which is the pathological feature of Parkinson's disease (PD). Resveratrol (Res), a polyphenol derived from grapes and blueberries, has been reported to reduce oxidative stress injury and to restore mitochondrial function. In this study, we aimed to explore the underlying molecular mechanism of the beneficial effects of Res against MPP+- induced mitochondrial dysfunction and cell apoptosis in SN4741 cells. The data showed that Res significantly alleviated MPP+- induce cytotoxicity and restored MPP+- induced mitochondrial dysfunction in SN4741 cells...
November 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27893608/ape1-protects-against-mpp-induced-neurotoxicity-through-erk1-2-signaling-in-pc12-cells
#15
Bei Kang, Shengzhi Mu, Qian Yang, Shenglong Guo, Xiaoli Chen, Hena Guo
Oxidative stress, induced by reactive oxygen species (ROS), is an apoptosis activator. Oxidative stress causes dopaminergic neuron loss and plays a pivotal role in the pathogenesis of Parkinson's disease (PD). A recent study showed that apurinic/apyrimidinic endonuclease 1 (Ape1) decreases cytotoxicity and promotes neuron survival under oxidative stress. Furthermore, it has been proven that Ape1 is involved in the pathogenesis of PD. However, little is known about the contribution of Ape1 toward the development of PD...
January 1, 2017: Neuroreport
https://www.readbyqxmd.com/read/27893607/acupuncture-does-not-protect-against-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-damage-of-dopaminergic-neurons-in-a-preclinical-mouse-model-of-parkinson-s-disease
#16
Hui-Jun Yang, Yu Gao, Ji Young Yun, Young Eun Kim, Gwanhee Ehm, Ji Yeon Lee, Min-Yung Yoon, Young-Shin Lee, Han-Joon Kim, Beomseok Jeon
Acupuncture treatment, a complementary and alternative medicine, is associated with a suggested neuroprotective effect in previous preclinical studies of Parkinson's disease (PD); however, results from human clinical trials have been mixed or unsuccessful. Recent systematic reviews of translational neuroprotective studies showed that the supposed efficacy is confounded by low methodological quality, particularly by a lack of randomization and concealed allocation. We sought to replicate previous experimental findings with a study design that mitigates the introduction of bias, including randomization, blinded outcome measures, sham acupuncture application, and allocation concealment by blinded neurotoxin administration...
January 1, 2017: Neuroreport
https://www.readbyqxmd.com/read/27890431/neuroprotective-mechanisms-of-plant-extracts-against-mptp-induced-neurotoxicity-future-applications-in-parkinson-s-disease
#17
REVIEW
Abdelrahman Ibrahim Abushouk, Ahmed Negida, Hussien Ahmed, Mohamed M Abdel-Daim
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models...
November 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27889907/activation-of-nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death
#18
Tian-Ya Liu, Xiao-Ying Yang, Long-Tai Zheng, Guang-Hui Wang, Xue-Chu Zhen
Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied with microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental MPTP-PD mouse model. Nur77 overexpression or application of Nur77 agonist CsnB suppressed the expression of proinflammatory genes, such as iNOS, COX-2, IL-1β, and TNF-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27886263/nicotinic-and-opioid-receptor-regulation-of-striatal-dopamine-d2-receptor-mediated-transmission
#19
Aphroditi A Mamaligas, Yuan Cai, Christopher P Ford
In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke dopamine release through this pathway. The frequency-dependence of disynaptic nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass filter in the dopaminergic microcircuit. Here, we used optogenetics to selectively stimulate either ChIs or dopamine terminals directly in the striatum...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886004/influence-of-surface-roughness-on-neural-differentiation-of-human-induced-pluripotent-stem-cells
#20
Zhengdong Li, Weiwei Wang, Karl Kratz, Judit Küchler, Xun Xu, Jie Zou, Deng Zijun, Xianlei Sun, Manfred Gossen, Nan Ma, Andreas Lendlein
Induced pluripotent stem cells (iPSCs) own the capacity to develop into all cell types of the adult body, presenting high potential in regenerative medicine. Regulating and controlling the differentiation of iPSCs using the surface topographic cues of biomaterials is a promising and safe approach to enhance their therapeutic efficacy. In this study, we tested the effects of surface roughness on differentiation of human iPSCs into neural progenitor cells and dopaminergic neuron cells using polystyrene with different roughness (R0: flat surface; R1: rough surface, Rq ∼ 6 μm; R2: rough surface, Rq ∼ 38 μm)...
November 23, 2016: Clinical Hemorheology and Microcirculation
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