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https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#1
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29331072/transcranial-ultrasonographic-image-analysis-system-for-decision-support-in-parkinson-disease
#2
Andrius Sakalauskas, Vita Špečkauskienė, Kristina Laučkaitė, Rytis Jurkonis, Daiva Rastenytė, Arūnas Lukoševičius
OBJECTIVES: Transcranial ultrasonography (US) is a relatively new neuroimaging modality proposed for early diagnostics of Parkinson disease (PD). The main limitation of transcranial US image-based diagnostics is a high degree of subjectivity caused by low quality of the transcranial images. The article presents a developed image analysis system and evaluates the potential of automated image analysis on transcranial US. METHODS: The system consists of algorithms for the segmentation and assessment of informative brain regions (midbrain and substantia nigra) and a decision support subsystem, which is equipped with 64 classification algorithms...
January 13, 2018: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/29330884/synapsin-iii-is-a-key-component-of-%C3%AE-synuclein-fibrils-in-lewy-bodies-of-pd-brains
#3
Francesca Longhena, Gaia Faustini, Tatiana Varanita, Michela Zaltieri, Vanessa Porrini, Isabella Tessari, Pietro Luigi Poliani, Cristina Missale, Barbara Borroni, Alessandro Padovani, Luigi Bubacco, Marina Pizzi, PierFranco Spano, Arianna Bellucci
Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III...
January 13, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29329678/apelin-13-ameliorates-cognitive-impairments-in-6-hydroxydopamine-induced-substantia-nigra-lesion-in-rats
#4
Elham Haghparast, Saeed Esmaeili-Mahani, Mehdi Abbasnejad, Vahid Sheibani
Although Parkinson's disease (PD) is well known with its motor deficits, the patients often suffer from cognitive dysfunction. Apelin, as the endogenous ligand of the APJ receptor, is found in several brain regions such as substantia nigra and mesolimbic pathway. However, the role of apelin in cognition and cognitive disorders has not been fully clarified. In this study the effects of apelin-13 were investigated on cognitive disorders in rat Parkinsonism experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the substantia nigra...
January 5, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29329581/microrna-124-regulates-the-expression-of-mekk3-in-the-inflammatory-pathogenesis-of-parkinson-s-disease
#5
Longping Yao, Yongyi Ye, Hengxu Mao, Fengfei Lu, Xiaozheng He, Guohui Lu, Shizhong Zhang
BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29323027/micrornas-in-parkinson-s-disease-and-emerging-therapeutic-targets
#6
REVIEW
Bridget Martinez, Philip V Peplow
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#7
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29319169/cell-tracking-survival-and-differentiation-capacity-of-adipose-derived-stem-cells-after-engraftment-in-rat-tissue
#8
Mario F Muñoz, Sandro Argüelles, Matias Guzman-Chozas, Remedios Guillén-Sanz, Jaime M Franco, José A Pintor-Toro, Mercedes Cano, Antonio Ayala
Adipose tissue is an important source of adipose derived stem cells (ADSCs). These cells have the potential of being used for certain therapies, in which the main objective is to recover the function of a tissue/organ affected by a disease. In order to contribute to repair of the tissue, these cells should be able to survive and carry out their functions in unfavorable conditions after being transplanted. This process requires a better understanding of the biology involved: such as the time cells remain in the implant site, how long they stay there, and whether or not they differentiate into host tissue cells...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29315562/hfe-genotype-restricts-the-response-to-paraquat-in-a-mouse-model-of-neurotoxicity
#9
Anne M Nixon, Mark D Meadowcroft, Elizabeth B Neely, Amanda M Snyder, Carson J Purnell, Justin Wright, Regina Lamendella, Wint Nandar, Xuemei Huang, James R Connor
Parkinson's disease (PD) is marked clinically by motor dysfunction and pathologically by dopaminergic cell loss in the substantia nigra (SN) and iron accumulation in the substantia nigra. The driver underlying iron accumulation is unknown and could be genetic or environmental. The HFE protein is critical for the regulation of cellular iron uptake. Mutations within this protein are associated with increased iron accumulation including in the brain. We have focused on the commonly occurring H63D variant of the HFE gene as a disease modifier in a number of neurodegenerative diseases...
January 8, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29315364/200-years-of-parkinson-s-disease-what-have-we-learnt-from-james-parkinson
#10
Claire McDonald, Gavin Gordon, Annette Hand, Richard W Walker, James M Fisher
2017 marks 200 years since James Parkinson's published his 'Essay on the Shaking Palsy'. Although now most famous for describing the condition that came to bear his name, Parkinson had a wide range of interests and his influence spread beyond medicine. In this review, we provide a biography of James Parkinson's remarkable life.Parkinson's paper not only comprehensively described the symptoms of Parkinson's disease (PD), but challenged his peers to better understand the pathophysiology of the PD. Key observation over the next 2 centuries, included the recognition of the link between the substantia nigra and PD and the discoveries of dopamine deficiency in patients with PD...
January 5, 2018: Age and Ageing
https://www.readbyqxmd.com/read/29314464/chemogenetic-inhibition-of-direct-pathway-striatal-neurons-normalizes-pathological-cue-induced-reinstatement-of-drug-seeking-in-rats
#11
Lindsay M Yager, Aaron F Garcia, Elizabeth A Donckels, Susan M Ferguson
Addiction to drugs such as cocaine is marked by cycles of compulsive drug-taking and drug-seeking behavior. Although the transition to addiction is thought to recruit neural processes in dorsal striatum, little is known regarding the role of dorsal striatal projections to the substantia nigra (i.e. the direct pathway) in regulating these behaviors. Combining a Cre-recombinase-dependent chemogenetic approach with a cocaine self-administration paradigm that produces both low-risk and high-risk addiction phenotypes, we examined the effect of transiently decreasing direct pathway activity in the dorsomedial striatum on drug-taking and drug-seeking under conditions of normal and pathological drug use...
January 5, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29311685/synaptotagmin-11-is-a-critical-mediator-of-parkin-linked-neurotoxicity-and-parkinson-s-disease-like-pathology
#12
Changhe Wang, Xinjiang Kang, Li Zhou, Zuying Chai, Qihui Wu, Rong Huang, Huadong Xu, Meiqin Hu, Xiaoxuan Sun, Suhua Sun, Jie Li, Ruiying Jiao, Panli Zuo, Lianghong Zheng, Zhenyu Yue, Zhuan Zhou
Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29310519/intranasal-stem-cell-treatment-as-a-novel-therapy-for-subarachnoid-hemorrhage
#13
Cora H Nijboer, Elke Kooijman, Cindy T van Velthoven, Erik Van Tilborg, Ivo A Tiebosch, Niels Eijkelkamp, Rick M Dijkhuizen, Jozef Kesecioglu, Cobi Heijnen
Subarachnoid hemorrhage (SAH) represents a major health problem in Western society due to high mortality and morbidity, and the relative young age of patients. Currently, efficacious therapeutic options are very limited. Mesenchymal stem cell (MSC) administration has been shown to improve functional outcome and lesion size in experimental models of stroke and neonatal hypoxic-ischemic brain injury. Here we studied the therapeutic potential of intranasally administered bone marrow-derived MSCs relatively late post-insult using a rat endovascular puncture model for SAH...
January 8, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29307665/effects-of-ketamine-on-vocal-impairment-gait-changes-and-anhedonia-induced-by-bilateral-6-ohda-infusion-into-the-substantia-nigra-pars-compacta-in-rats-therapeutic-implications-for-parkinson-s-disease
#14
Débora Dalla Vecchia, Luiz Kae Sales Kanazawa, Etiéli Wendler, Palloma de Almeida Soares Hocayen, Estevan Bruginski, Francinete Ramos Campos, Cristina Aparecida Jark Stern, Maria Aparecida Barbato Frazão Vital, Edmar Miyoshi, Markus Wöhr, Rainer K W Schwarting, Roberto Andreatini
Parkinson's disease is a chronic neurodegenerative disorder characterized by cardinal motor features, such as bradykinesia, but also vocal deficits (e.g. difficulties to articulate words and to keep the tone of voice) and depression. In the present study, rats with bilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta were evaluated for changes in the emission of 50-kHz ultrasonic vocalizations, gait impairment (catwalk test), and depressive-like behaviour (sucrose preference test).Furthermore, we evaluated the effect of repeated treatment (28 days) with ketamine (5, 10, and 15 mg/kg, ip, once per week) or imipramine (15 mg/kg, ip, daily)...
January 4, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29307543/neurotensin-speeds-inhibition-of-dopamine-neurons-through-temporal-modulation-of-gabaa-and-gabab-receptor-mediated-synaptic-input
#15
Christopher W Tschumi, Michael J Beckstead
Midbrain dopamine neurons play physiological roles in many processes including reward learning and motivated behavior, and are tonically inhibited by γ-aminobutyric acid (GABA)ergic input from multiple brain regions. Neurotensin (NT) is a neuropeptide which acutely modulates midbrain dopamine neuron excitability through multiple mechanisms, one of which is a decrease of GABA-mediated inhibition. However, the mechanisms through which NT depresses GABA signaling are not known. Here we used whole cell patch-clamp electrophysiology of dopamine neurons in mouse brain slices to show that NT acts both presynaptically to increase GABAA and postsynaptically to decrease GABAB receptor-mediated currents in the substantia nigra...
January 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29305898/tyrosine-hydroxylase-afferents-to-the-interstitial-nucleus-of-the-posterior-limb-of-the-anterior-commissure-are-neurochemically-distinct-from-those-projecting-to-neighboring-nuclei
#16
Tsuyoshi Yamaguchi, Ayuka Ehara, Kazuhiko Nakadate, Shuichi Ueda
The interstitial nucleus of the posterior limb of the anterior commissure (IPAC) is exclusively innervated by tyrosine hydroxylase-immunoreactive (TH-IR) fibers as observed in the other nuclei of the rat forebrain such as the striatum and nucleus accumbens. Distinguishing TH-IR afferents to the IPAC from those projecting to neighboring nuclei has been difficult. However, we previously showed that the TH-IR fibers projecting to the IPAC were invulnerable to neurodegeneration in zitter mutant rats, whereas almost all TH-IR afferents fibers to the dorsolateral striatum were lost, indicating that these two groups of TH-IR afferents have distinct neurochemical properties...
January 3, 2018: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29305892/the-involvement-of-the-pathway-connecting-the-substantia-nigra-the-periaqueductal-gray-matter-and-the-retrotrapezoid-nucleus-in-breathing-control-in-a-rat-model-of-parkinson-s-disease
#17
Juliana C Lima, Luiz M Oliveira, Marina T Botelho, Thiago S Moreira, Ana C Takakura
Parkinson's disease (PD) is characterized by a reduction in the number of dopaminergic neurons of the substantia nigra (SNpc), accompanied by motor and non-motor deficiencies such as respiratory failure. Here, our aim was to investigate possible neuronal communications between the SNpc and chemoreceptor neurons within the retrotrapezoid nucleus (RTN), in order to explain neurodegeneration and the loss of breathing function in the 6-OHDA PD animal model. Male Wistar rats received tracer injections in the SNpc, RTN and periaqueductal gray (PAG) regions to investigate the projections between those regions...
January 4, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29305570/neurotrophic-factors-hold-promise-for-the-future-of-parkinson-s-disease-treatment-is-there-a-light-at-the-end-of-the-tunnel
#18
Ava Nasrolahi, Javad Mahmoudi, Abolfazl Akbarzadeh, Mohammad Karimipour, Saeed Sadigh-Eteghad, Roya Salehi, Mehdi Farhoudi
Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by a spectrum of clinicopathologic signs and a complex etiology. PD results from the degeneration of dopaminergic (DAergic) neurons in the substantia nigra. Current therapies for PD are only able to alleviate symptoms without stopping disease progression. In addition, the available therapeutic strategies do not have long-lasting effects. Furthermore, these therapies cause different ranges of adverse side effects...
January 6, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29304113/discovery-of-indolylpiperazinylpyrimidines-with-dual-target-profiles-at-adenosine-a2a-and-dopamine-d2-receptors-for-parkinson-s-disease-treatment
#19
Yi-Ming Shao, Xiaohua Ma, Priyankar Paira, Aaron Tan, Deron Raymond Herr, Kah Leong Lim, Chee Hoe Ng, Gopalakrishnan Venkatesan, Karl-Norbert Klotz, Stephanie Federico, Giampiero Spalluto, Siew Lee Cheong, Yu Zong Chen, Giorgia Pastorin
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects...
2018: PloS One
https://www.readbyqxmd.com/read/29298733/progressive-striatonigral-degeneration%C3%A2-in-a-transgenic-mouse-model-of-multiple-system-atrophy-translational-implications-for-interventional-therapies
#20
Violetta Refolo, Francesco Bez, Alexia Polissidis, Daniela Kuzdas-Wood, Edith Sturm, Martina Kamaratou, Werner Poewe, Leonidas Stefanis, M Angela Cenci, Marina Romero-Ramos, Gregor K Wenning, Nadia Stefanova
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by widespread oligodendroglial cytoplasmic inclusions of filamentous α-synuclein, and neuronal loss in autonomic centres, basal ganglia and cerebellar circuits. It has been suggested that primary oligodendroglial α-synucleinopathy may represent a trigger in the pathogenesis of MSA, but the mechanisms underlying selective vulnerability and disease progression are unclear. The post-mortem analysis of MSA brains provides a static final picture of the disease neuropathology, but gives no clear indication on the sequence of pathogenic events in MSA...
January 3, 2018: Acta Neuropathologica Communications
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