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https://www.readbyqxmd.com/read/27931506/neural-stem-cells-derived-from-human-parthenogenetic-stem-cells-engraft-and-promote-recovery-in-a-nonhuman-primate-model-of-parkinsons-disease
#1
Rodolfo Gonzalez, Ibon Garitaonandia, Maxim Poustovoitov, Tatiana Abramihina, Caleb McEntire, Ben Culp, Jordan Attwood, Alexander Noskov, Trudy Christiansen-Weber, Marwa Khater, Sergio Mora-Castilla, Cuong To, Andrew Crain, Glenn Sherman, Andrey Semechkin, Louise C Laurent, John D Elsworth, John Sladek, Evan Y Snyder, D Eugene Redmond, Russell A Kern
Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinsons disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying potentially viable human embryos and can be used to generate an unlimited supply of neural cells for transplantation...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27930324/dopamine-release-from-the-locus-coeruleus-to-the-dorsal-hippocampus-promotes-spatial-learning-and-memory
#2
Kimberly A Kempadoo, Eugene V Mosharov, Se Joon Choi, David Sulzer, Eric R Kandel
Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC)...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929474/a-simple-one-step-dissection-protocol-for-whole-mount-preparation-of-adult-drosophila-brains
#3
Antonio J Tito, Shebna Cheema, Mian Jiang, Sheng Zhang
There is an increasing interest in using Drosophila to model human brain degenerative diseases, map neuronal circuitries in adult brains, and study the molecular and cellular basis of higher brain functions. A whole-mount preparation of adult brains with well-preserved morphology is critical for such whole brain-based studies, but can be technically challenging and time-consuming. This protocol describes an easy-to-learn, one-step dissection approach of an adult fly head in less than 10 s, while keeping the intact brain attached to the rest of the body to facilitate subsequent processing steps...
December 1, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27928963/role-of-neurotrophic-factors-in-parkinson%C3%A2-s-disease
#4
Diogo Tomé, Carla Pais Fonseca, Filipa Lopes Campos, Graça Baltazar
Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels...
December 8, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27928028/mitochondrial-pyruvate-carrier-regulates-autophagy-inflammation-and-neurodegeneration-in-experimental-models-of-parkinson-s-disease
#5
Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N Hildebrandt, Jennifer A Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, William G McDonald, Martha L Escobar Galvis, Jeffrey H Kordower, Jeremy M Van Raamsdonk, Jerry R Colca, Patrik Brundin
Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium (MPP(+)) insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein-based Caenorhabditis elegans model...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927963/inhibition-of-prolyl-oligopeptidase-restores-spontaneous-motor-behavior-in-the-%C3%AE-synuclein-virus-vector-based-parkinson-s-disease-mouse-model-by-decreasing-%C3%AE-synuclein-oligomeric-species-in-mouse-brain
#6
Reinis Svarcbahs, Ulrika H Julku, Timo T Myöhänen
: Decreased clearance of α-synuclein (aSyn) and aSyn protein misfolding and aggregation are seen as major factors in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies that leads to disruption in neuronal function and eventually to cell death. Prolyl oligopeptidase (PREP) can accelerate the aSyn aggregation process, while inhibition of PREP by a small molecule inhibitor decreases aSyn oligomer formation and enhances its clearance via autophagy in different aSyn overexpressing cell types and in transgenic PD animal models...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27927785/dopaminergic-treatment-weakens-medium-spiny-neuron-collateral-inhibition-in-the-parkinsonian-striatum
#7
Wei Wei, Shengyuan Ding, Fu-Ming Zhou
The striatal medium spiny neurons (MSNs) are critical to both motor and cognitive functions. A potential regulator of MSN activity is the GABAergic collateral axonal input from neighboring MSNs. These collateral axon terminals are further under the regulation of presynaptic dopamine (DA) receptors that may become dysfunctional when the intense striatal DA innervation is lost in Parkinson's disease (PD). We show here that DA D1 receptor-expressing MSNs (D1-MSNs) and D2 receptor-expressing MSNs (D2-MSNs) each formed high rate, one-way collateral connections with a homotypic preference in both normal and DA-denervated mouse striatum...
December 7, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27927222/tollip-an-early-regulator-of-the-acute-inflammatory-response-in-the-substantia-nigra
#8
Marie Humbert-Claude, D Duc, D Dwir, L Thieren, J Sandström von Tobel, C Begka, F Legueux, D Velin, M H Maillard, K Q Do, F Monnet-Tschudi, L Tenenbaum
BACKGROUND: Tollip is a ubiquitously expressed protein, originally described as a modulator of the IL-1R/TLR-NF-κB signaling pathways. Although this property has been well characterized in peripheral cells, and despite some evidence of its expression in the central nervous system, the role of Tollip in neuroinflammation remains poorly understood. The present study sought to explore the implication of Tollip in inflammation in the substantia nigra pars compacta, the structure affected in Parkinson's disease...
December 7, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27926449/the-role-of-dopamine-in-the-pathophysiology-and-treatment-of-apathy
#9
T T-J Chong, M Husain
Disorders of diminished motivation, such as apathy, are common and prevalent across a wide range of medical conditions, including Parkinson's disease, Alzheimer's dementia, stroke, depression, and schizophrenia. Such disorders have a significant impact on morbidity and quality of life, yet their management lacks consensus and remains unsatisfactory. Here, we review laboratory and clinical evidence for the use of dopaminergic therapies in the treatment of apathy. Dopamine is a key neurotransmitter that regulates motivated decision making in humans and other species...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27922638/enhancing-dopaminergic-signaling-and-histone-acetylation-promotes-long-term-rescue-of-deficient-fear-extinction
#10
N Whittle, V Maurer, C Murphy, J Rainer, D Bindreither, M Hauschild, A Scharinger, M Oberhauser, T Keil, C Brehm, T Valovka, J Striessnig, N Singewald
Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27919828/mucuna-pruriens-reduces-inducible-nitric-oxide-synthase-expression-in-parkinsonian-mice-model
#11
Satyndra Kumar Yadav, Sachchida Nand Rai, Surya Pratap Singh
Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp...
December 2, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27917933/inhibition-of-alpha-synuclein-aggregation-by-multifunctional-dopamine-agonists-assessed-by-a-novel-in-vitro-assay-and-an-in-vivo-drosophila-synucleinopathy-model
#12
Deepthi Yedlapudi, Gnanada S Joshi, Dan Luo, Sokol V Todi, Aloke K Dutta
Aggregation of alpha synuclein (α-syn) leading to dopaminergic neuronal death has been recognized as one of the main pathogenic factors in the initiation and progression of Parkinson's disease (PD). Consequently, α-syn has been targeted for the development of therapeutics for PD. We have developed a novel assay to screen compounds with α-syn modulating properties by mimicking recent findings from in vivo animal studies involving intrastriatal administration of pre-formed fibrils in mice, resulting in increased α-syn pathology accompanying the formation of Lewy-body (LB) type inclusions...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27915043/involvement-of-bdnf-trkb-signaling-in-the-effect-of-diphenyl-diselenide-on-motor-function-in-a-parkinson-s-disease-rat-model
#13
Tuane Bazanella Sampaio, Simone Pinton, Juliana Trevisan da Rocha, Bibiana Mozzaquatro Gai, Cristina Wayne Nogueira
Parkinson's disease is a progressive neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons. Diphenyl diselenide [(PhSe)2] is a compound with pharmacological proprieties, such as antidepressant and neuroprotective. Therefore, this study investigated whether (PhSe)2 reverses motor impairment and neurochemical alterations in a model of Parkinson's disease induced by 6-hydroxydopamine (6-OHDA) in rats. For this, male Wistar rats received 20μg/3μl of 6-OHDA or vehicle into the right striatum...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27914942/is-there-a-role-for-ghrelin-in-central-dopaminergic-systems-focus-on-nigrostriatal-and-mesocorticolimbic-pathways
#14
REVIEW
Alicia Stievenard, Mathieu Méquinion, Zane B Andrews, Alain Destée, Marie-Christine Chartier-Harlin, Odile Viltart, Christel C Vanbesien-Mailliot
The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer. Ghrelin and its receptor, which is expressed throughout the brain, play an important role in motivation and reward. Ghrelin finely modulates the mesencephalic dopaminergic signaling and is thus currently studied in pathological conditions including dopamine-related disorders...
November 30, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27914807/phosphorylation-of-p53-by-lrrk2-induces-microglial-tumor-necrosis-factor-%C3%AE-mediated-neurotoxicity
#15
Dong Hwan Ho, Wongi Seol, Jin Hwan Eun, Il-Hong Son
Leucine-rich repeat kinase (LRRK2), a major causal gene of Parkinson's disease (PD), functions as a kinase. The most prevalent mutation of LRRK2 is G2019S. It exhibits increased kinase activity compared to the wildtype LRRK2. Previous studies have shown that LRRK2 can phosphorylate p53 at T304 and T377 of threonine-X-arginine (TXR) motif in neurons. Reduction of LRRK2 expression or inhibition of LRRK2 kinase activity has been shown to be able to alleviate LPS-induced neuroinflammation in microglia cells. In this study, we found that LRRK2 could also phosphorylate p53 in microglia model BV2 cells...
November 30, 2016: Biochemical and Biophysical Research Communications
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
#16
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
#17
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
#18
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
#19
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
#20
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
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