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https://www.readbyqxmd.com/read/29792933/role-of-neuronal-nitric-oxide-synthase-in-slowly-progressive-dopaminergic-neurodegeneration-in-the-zitter-rat
#1
Ayuka Ehara, Kazuhiko Nakadate, Hiroyuki Sugimoto, Kanji Yoshimoto, Shuichi Ueda
Neuronal nitric oxide synthase (nNOS) is involved in nigrostriatal dopaminergic (DA) neurodegeneration. However, little is known about the distribution patterns and functions of nNOS in slowly progressive DA neurodegeneration. Here we describe the spatiotemporal change in nNOS expression over the course of neurodegeneration and the effect of short- or long-term treatment with the nNOS inhibitor, 7-nitroindazole (7-NI), in zitter (zi/zi) rats. In the substantia nigra pars compacta (SNc), nNOS expression was significantly increased with progression of neurodegeneration...
May 21, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29792848/subthalamic-nucleus-deep-brain-stimulation-protects-neurons-by-activating-autophagy-via-pp2a-inactivation-in-a-rat-model-of-parkinson-s-disease
#2
Ting-Ting Du, Ying-Chuan Chen, Yong-Quan Lu, Fan-Gang Meng, Hui Yang, Jian-Guo Zhang
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum...
May 21, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#3
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29789702/parallel-descending-dopaminergic-connectivity-of-a13-cells-to-the-brainstem-locomotor-centers
#4
Sandeep Sharma, Linda H Kim, Kyle A Mayr, David A Elliott, Patrick J Whelan
The mesencephalic locomotor region (MLR) is an important integrative area for the initiation and modulation of locomotion. Recently it has been realized that dopamine (DA) projections from the substantia nigra pars compacta project to the MLR. Here we explore DA projections from an area of the medial zona incerta (ZI) known for its role in motor control onto the MLR. We provide evidence that dopaminergic (DAergic) A13 neurons have connectivity to the cuneiform nucleus (CnF) and pedunculopontine tegmental nucleus (PPTg) of the MLR...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29788902/dystonia-deafness-syndrome-caused-by-actb-p-arg183trp-heterozygosity-shows-striatal-dopaminergic-dysfunction-and-response-to-pallidal-stimulation
#5
Inger Marie Skogseid, Oddveig Røsby, Ane Konglund, James P Connelly, Bård Nedregaard, Greg Eigner Jablonski, Nadja Kvernmo, Asbjørg Stray-Pedersen, Joel C Glover
BACKGROUND: Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally...
May 22, 2018: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#6
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29786085/chronic-crh-depletion-from-gabaergic-long-range-projection-neurons-in-the-extended-amygdala-reduces-dopamine-release-and-increases-anxiety
#7
Nina Dedic, Claudia Kühne, Mira Jakovcevski, Jakob Hartmann, Andreas J Genewsky, Karina S Gomes, Elmira Anderzhanova, Max L Pöhlmann, Simon Chang, Adam Kolarz, Annette M Vogl, Julien Dine, Michael W Metzger, Bianca Schmid, Rafael C Almada, Kerry J Ressler, Carsten T Wotjak, Valery Grinevich, Alon Chen, Mathias V Schmidt, Wolfgang Wurst, Damian Refojo, Jan M Deussing
The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release...
May 21, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#8
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785351/genetic-inactivation-of-alpha-synuclein-affects-embryonic-development-of-dopaminergic-neurons-of-the-substantia-nigra-but-not-the-ventral-tegmental-area-in-mouse-brain
#9
Tatiana V Tarasova, Olga A Lytkina, Valeria V Goloborshcheva, Larisa N Skuratovskaya, Alexandr I Antohin, Ruslan K Ovchinnikov, Michail S Kukharsky
Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration...
2018: PeerJ
https://www.readbyqxmd.com/read/29785199/physical-exercise-for-parkinson-s-disease-clinical-and-experimental-evidence
#10
REVIEW
Alessandro Oliveira de Carvalho, Alberto Souza Sá Filho, Eric Murillo-Rodriguez, Nuno Barbosa Rocha, Mauro Giovanni Carta, Sergio Machado
Background: National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. Objective: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
https://www.readbyqxmd.com/read/29783988/tolerogenic-bone-marrow-derived-dendritic-cells-induce-neuroprotective-regulatory-t-cells-in-a-model-of-parkinson-s-disease
#11
Charles R Schutt, Howard E Gendelman, R Lee Mosley
BACKGROUND: Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Recently, we demonstrated in an early phase 1 clinical trial that GM-CSF also improves motor skills in PD patients. However, the mechanisms of Treg induction and its effects on neuroprotective responses remain unknown...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29783725/polyphenols-in-parkinson-s-disease-a-systematic-review-of-in-vivo-studies
#12
REVIEW
Małgorzata Kujawska, Jadwiga Jodynis-Liebert
Parkinson's disease (PD) is the second most common neurodegenerative disorder. However, therapeutic options treating only its symptoms are very disappointing. Therefore there is an ongoing search for compounds capable of tackling the multi-dimensional features of PD. Recently natural polyphenols have gained great interest as potential therapeutic agents. Herein, we have attempted to summarize results obtained in different animal models demonstrating their neuroprotective effects. The in vivo findings presented below are supported by human subject data and reports regarding the ability of polyphenols to cross the blood-brain barrier...
May 19, 2018: Nutrients
https://www.readbyqxmd.com/read/29783643/hydroxysafflor-yellow-a-attenuates-lipopolysaccharide-induced-neurotoxicity-and-neuroinflammation-in-primary-mesencephalic-cultures
#13
Tian Wang, Yu-Xin Ding, Jie He, Cheng-Jun Ma, Yue Zhao, Zhen-Hua Wang, Bing Han
Lipopolysaccharide (LPS)-induced neuroinflammation triggers and accelerates the pathogenesis of Parkinson's disease (PD). Carthamus tinctorius L., a traditional Chinese medicine, has been widely used for the treatment of cerebrovascular disease. Hydroxysafflor Yellow A (HSYA) is an active component of C. tinctorius . The purpose of this study was to investigate whether HSYA could attenuate LPS-induced neurotoxicity and neuroinflammation in primary mesencephalic cultures. Cell viability was measured by MTT and LDH assays...
May 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29782623/astrocytic-hypertrophy-in-the-rat-ventral-tegmental-area-following-chronic-morphine-differs-with-age
#14
Emily C Goins, Dusica Bajic
The ventral tegmental area (VTA) is the origin of the mesolimbic dopaminergic system known to play an integral role in mediating reward and development of drug addiction. Although the differences in neuronal plasticity of VTA at various ages remain to be understood, age is known to influence the effects of chronic opioids. In addition, adaptations associated with exposure to opioids within glial populations located in the VTA are poorly understood. The objective of the study was to determine if there are changes in astrocytic immunofluorescent labeling in the VTA following chronic morphine administration in a rat model at different ages: newborn at postnatal day (PD)7 and adult (estimated PD57)...
2018: Journal of neurology and neurorehabilitation research
https://www.readbyqxmd.com/read/29781098/pet-imaging-of-the-influence-of-physiological-and-pathological-%C3%AE-synuclein-on-dopaminergic-and-serotonergic-neurotransmission-in-mouse-models
#15
Elise Levigoureux, Caroline Bouillot, Thierry Baron, Luc Zimmer, Sophie Lancelot
AIMS: Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of neurodegenerative synucleinopathies. This in vivo study explored glucose metabolism and dopaminergic and serotoninergic neurotransmission in KO α-syn, wild-type mice and an accelerated murine model of synucleinopathy (M83). METHODS: MicroPET acquisitions were performed in all animals aged 5-6 months using five radiotracers exploring brain glucose metabolism ([18 F]FDG), dopamine neurotransmission ([11 C]raclopride, [11 C]PE2I) and serotonin neurotransmission ([18 F]MPPF, [11 C]DASB)...
May 20, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29780881/nucleus-accumbens-microcircuit-underlying-d2-msn-driven-increase-in-motivation
#16
Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, Ana João Rodrigues
The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29779874/a-gabaergic-feedback-shapes-dopaminergic-input-on-the-drosophila-mushroom-body-to-promote-appetitive-long-term-memory
#17
Alice Pavlowsky, Johann Schor, Pierre-Yves Plaçais, Thomas Preat
Memory consolidation is a crucial step for long-term memory (LTM) storage. However, we still lack a clear picture of how memory consolidation is regulated at the neuronal circuit level. Here, we took advantage of the well-described anatomy of the Drosophila olfactory memory center, the mushroom body (MB), to address this question in the context of appetitive LTM. The MB lobes, which are made by the fascicled axons of the MB intrinsic neurons, are organized into discrete anatomical modules, each covered by the terminals of a defined type of dopaminergic neuron (DAN) and the dendrites of a corresponding type of MB output neuron (MBON)...
May 9, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29779176/intranasal-delivery-of-pgdnf-dna-nanoparticles-provides-neuroprotection-in-the-rat-6-hydroxydopamine-model-of-parkinson-s-disease
#18
Amirah E-E Aly, Brendan T Harmon, Linas Padegimas, Ozge Sesenoglu-Laird, Mark J Cooper, Barbara L Waszczak
Glial cell line-derived neurotrophic factor (GDNF) gene therapy could offer a disease-modifying treatment for Parkinson's disease (PD). Here, we report that plasmid DNA nanoparticles (NPs) encoding human GDNF administered intranasally to rats induce transgene expression in the brain and protect dopamine neurons in a model of PD. To first test whether intranasal administration could transfect cells in the brain, rats were sacrificed 1 week after intranasal pGDNF NPs or the naked plasmid. GDNF ELISA revealed significant increases in GDNF expression throughout the brain for both treatments...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29779156/adolescent-isolation-rearing-produces-a-prepulse-inhibition-deficit-correlated-with-expression-of-the-nmda-glun1-subunit-in-the-nucleus-accumbens
#19
Megan L Fitzgerald, Virginia M Pickel
Adolescence is a transition period during which social interaction is necessary for normal brain and behavior development. Severely abnormal social interactions during adolescence can increase the incidence of lifelong psychiatric disease. Decreased prepulse inhibition (PPI) is a quantifiable hallmark of some psychiatric illnesses in humans and can be elicited in rodents by isolation rearing throughout the adolescent transition period. PPI is a measure of sensorimotor gating in which the nucleus accumbens (Acb) is crucially involved...
May 19, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29779103/dopamine-synthesis-as-a-mechanism-of-brain-plasticity-in-nigrostriatal-system-pathology
#20
A A Kolacheva, M V Ugrumov
Using an experimental Parkinson's disease model (symptoms develop in mice after the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), we studied the characteristics of the synthesis of dopamine as a possible compensatory mechanism aimed at maintaining the dopamine level in the dopaminergic neurons that survived in this pathology. We found no correlation between the content and activity of tyrosine hydroxylase in the nigrostriatal system. The enzyme activity and the dopamine content showed unidirectional changes in the substantia nigra, but not in the striatum, which is apparently due to triggering other compensatory mechanisms...
March 2018: Doklady. Biochemistry and Biophysics
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