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https://www.readbyqxmd.com/read/28431876/role-of-the-locus-coeruleus-catecholaminergic-neurons-in-the-chemosensory-control-of-breathing-in-a-parkinson-s-disease-model
#1
Luiz M Oliveira, Marina Tuppy, Thiago S Moreira, Ana C Takakura
A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia 40days after PD-induction. The functional deficiency is restored 60days after 6-OHDA injection and here we tested the hypothesis that the locus coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute Ventilation (VE) in response to hypercapnia (7% CO2) was assessed one day before, and then 40 and 60days after bilateral 6-OHDA (24μg/μL) or vehicle injections into the LC in control or PD-induced male Wistar rats...
April 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28412322/microrna-130b-transcriptionally-regulated-by-histone-h3-deacetylation-renders-akt-ubiquitination-and-apoptosis-resistance-to-6-ohda
#2
Liang Xu, Yu Jia, Xiang-Hong Yang, Fang Han, Yang Zheng, Yin Ni, Xu Chen, Jun Hong, Jing-Quan Liu, Qian Li, Ren-Hua Sun, Shi-Jing Mo
Apoptosis of DA neurons is a contributing cause of disability and death for Parkinson's disease (PD). Akt may become a potential therapeutic target for PD since Akt has been deactivated during DA neuron apoptosis. We previously demonstrated that Akt confers apoptosis resistance against 6-OHDA in DA neuron-like PC12 cells, yet the underlying mechanisms accounted for this are not fully understood. Here we report that microRNA-130b (miR-130b)-dependent and cylindromatosis (CYLD) repression-mediated Akt ubiquitination renders apoptosis resistance of PC12 cells to 6-OHDA, which elicits histone H3 deacetylation-induced transcriptional downregulation of miR-130b vice versa...
April 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28403913/brilliant-blue-g-but-not-fenofibrate-treatment-reverts-hemiparkinsonian-behavior-and-restores-dopamine-levels-in-an-animal-model-of-parkinson-s-disease
#3
Enéas G Ferrazoli, Héllio D N de Souza, Isis C Nascimento, Ágatha Oliveira-Giacomelli, Telma T Schwindt, Luiz R Britto, Henning Ulrich
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum. Several processes have been described as potential inducers of the dopaminergic neuron death, such as inflammation, oxidative stress, and mitochondrial dysfunction. However, the death of dopaminergic neurons seems to be multifactorial, and its cause remains unclear. ATP-activating purinergic receptors influence various physiological functions in the CNS, including neurotransmission...
April 13, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28398338/the-histamine-h3-receptor-antagonist-thioperamide-rescues-circadian-rhythm-and-memory-function-in-experimental-parkinsonism
#4
D Masini, C Lopes-Aguiar, A Bonito-Oliva, D Papadia, R Andersson, A Fisahn, G Fisone
Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine the effect of thioperamide, a histamine H3 receptor antagonist, on circadian activity, recognition memory and anxiety. A partial, bilateral 6-OHDA lesion of the striatum reduces motor activity during the active phase of the 24 h cycle...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28397192/effects-of-asarinin-on-dopamine-biosynthesis-and-6-hydroxydopamine-induced-cytotoxicity-in-pc12-cells
#5
Hyun Jin Park, Kyung Sook Lee, Ting Ting Zhao, Kyung Eun Lee, Myung Koo Lee
This study investigated the effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in rat adrenal pheochromocytoma (PC12) cells. Treatment with asarinin (25-50 μM) increased intracellular dopamine levels and enhanced L-DOPA-induced increases in dopamine levels. Asarinin (25 μM) induced cyclic AMP-dependent protein kinase A (PKA) signaling, leading to increased cyclic AMP-response element binding protein (CREB) and tyrosine hydroxylase (TH) phosphorylation, which in turn stimulated dopamine production...
April 10, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28390981/neurochemical-effects-of-the-r-form-of-%C3%AE-lipoic-acid-and-its-neuroprotective-mechanism-in-cellular-models-of-parkinson-s-disease
#6
Hong Zhao, Xingcheng Zhao, Lijuan Liu, Hongxu Zhang, Mingwen Xuan, Zhaohui Guo, Hongcai Wang, Chang Liu
OBJECTIVE: Parkinson's disease (PD) is a common neurodegenerative disease. This study aimed to investigate the effects of the R form of α-lipoic acid (RLA) in cellular models of PD induced by 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: Cell viability and apoptosis were detected using CCK8 and Annexin V-FITC assays, respectively. Intracellular reactive oxygen species (ROS) were detected by fluorescence staining. ELISA assays were performed to detect the levels of dopamine and α-synuclein...
April 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28390950/reduced-ability-of-calcitriol-to-promote-augmented-dopamine-release-in-the-lesioned-striatum-of-aged-rats
#7
Wayne A Cass, Laura E Peters
Parkinson's disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats...
April 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28390876/time-course-study-of-fractional-anisotropy-in-the-substantia-nigra-of-a-parkinsonian-rat-model-induced-by-6-ohda
#8
Wenzhong Zhang, Li Zhang, Limin Liu, Xiaomin Wang
Diffusion tensor imaging (DTI) is a non-invasive magnetic resonance imaging technique that can be used to assess microstructural changes in a brain disease such as Parkinson's disease (PD). Fractional anisotropy (FA) is a commonly used parameter in DTI analysis, although properties of DTI/FA in analyzing brain modifications in PD have been poorly profiled. This study was thus designed to characterize the detailed time course of FA in the substantia nigra (SN). A rat model of PD was induced by microinfusion of 6-OHDA into the right medial forebrain bundle...
April 5, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28385636/newborn-dopaminergic-neurons-are-associated-with-the-migration-and-differentiation-of-svz-derived-neural-progenitors-in-a-6-hydroxydopamin-injected-mouse-model
#9
M Q Xie, Z C Chen, P Zhang, H J Huang, T T Wang, Y-Q Ding, S S Qi, C Zhang, S X Chen, P Zhou, C C Shao, M Liao, C Y Sun
The use of the existing endogenous neural progenitor cells (NPCs) in the brains of adult mammalian animals is challenging for cell therapy in treating Parkinson's disease (PD). Previous studies have indicated that there is a low level of neurogenesis in the substantia nigra (SN) of adult mice. To assess the regenerative/neurogenic capacity of NPCs following an intranigral injection of 6-hydroxydopamine (6-OHDA), the proliferation and differentiation of subventricular zone (SVZ)- and midbrain-derived NPCs were investigated, and the origin of SN newborn dopaminergic neurons was traced by using Nestin-CreER(TM)::ROSA26-LacZ mice and constructing a plasmid CD133-Promoter2-Cre...
April 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28377741/adenosine-a2a-receptor-gene-knockout-prevents-l-3-4-dihydroxyphenylalanine-induced-dyskinesia-by-downregulation-of-striatal-gad67-in-6-ohda-lesioned-parkinson-s-mice
#10
Su-Bing Yin, Xiao-Guang Zhang, Shuang Chen, Wen-Ting Yang, Xia-Wei Zheng, Guo-Qing Zheng
l-3,4-Dihydroxyphenylalanine (l-DOPA) remains the primary pharmacological agent for the symptomatic treatment of Parkinson's disease (PD). However, the development of l-DOPA-induced dyskinesia (LID) limits the long-term use of l-DOPA for PD patients. Some data have reported that adenosine A2A receptor (A2AR) antagonists prevented LID in animal model of PD. However, the mechanism in which adenosine A2AR blockade alleviates the symptoms of LID has not been fully clarified. Here, we determined to knock out (KO) the gene of A2AR and explored the possible underlying mechanisms implicated in development of LID in a mouse model of PD...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28376279/molecular-mechanisms-underlying-protective-effects-of-quercetin-against-mitochondrial-dysfunction-and-progressive-dopaminergic-neurodegeneration-in-cell-culture-and-mitopark-transgenic-mouse-models-of-parkinson-s-disease
#11
Muhammet Ay, Jie Luo, Monica Langley, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Quercetin, one of the major flavonoids in plants, has been recently reported to have neuroprotective effects against neurodegenerative processes. However, since the molecular signaling mechanisms governing these effects are not well clarified, we evaluated quercetin's effect on the neuroprotective signaling events in dopaminergic neuronal models and further tested its efficacy in the MitoPark transgenic mouse model of Parkinson's disease (PD). Western blotting analysis revealed that quercetin significantly induced the activation of two major cell survival kinases, protein kinase D1 (PKD1) and Akt in MN9D dopaminergic neuronal cells...
April 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28363801/continuous-cerebroventricular-administration-of-dopamine-a-new-treatment-for-severe-dyskinesia-in-parkinson-s-disease
#12
C Laloux, F Gouel, C Lachaud, K Timmerman, B Do Van, A Jonneaux, M Petrault, G Garcon, N Rouaix, C Moreau, R Bordet, J A Duce, J C Devedjian, D Devos
In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia...
March 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28347345/serotonergic-system-in-hypoxic-ventilatory-response-in-unilateral-rat-model-of-parkinson-s-disease
#13
Kryspin Andrzejewski, Katarzyna Kaczyńska, Małgorzata Zaremba
BACKGROUND: Malfunctioning of the serotonergic system in Parkinson's disease may contribute to non-motor symptoms such as respiratory complications. Thus the aim of our study was to investigate the role of serotonin 5-HT2 receptors in the modulation of normoxic breathing and the hypoxic ventilatory response (HVR) in rat model of Parkinson's disease. METHODS: Wistar rats were lesioned unilaterally with double 6-hydroxydopamine (6-OHDA) injection to the right medial forebrain bundle (MFB)...
March 27, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28337120/antidyskinetic-effects-of-mek-inhibitor-are-associated-with-multiple-neurochemical-alterations-in-the-striatum-of-hemiparkinsonian-rats
#14
Guiqin Chen, Shuke Nie, Chao Han, Kai Ma, Yan Xu, Zhentao Zhang, Stella M Papa, Xuebing Cao
L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although, the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28328168/intrastriatal-transplantation-of-human-neural-stem-cells-restores-the-impaired-subventricular-zone-in-parkinsonian-mice
#15
Fuxing Zuo, Feng Xiong, Xia Wang, Xueyuan Li, Renzhi Wang, Wei Ge, Xinjie Bao
Cell replacement therapy using neural stem cells (NSCs) transplantation has recently emerged as a promising method of Parkinson's disease (PD) treatment; however, the underlying mechanisms are not fully understood. To gain new insights into the mechanisms of 6-hydroxydopamine (6-OHDA)-induced lesioning and therapeutic efficacy of human NSCs (hNSCs) transplantation, the striatum (ST) of intrastriatal 6-OHDA-injected parkinsonian mice were unilaterally engrafted with undifferentiated hNSCs. A high-throughput quantitative proteomic approach was used to characterize the proteome profiles of PD-related brain regions such as the SN, ST, olfactory bulb, and subventricular zone (SVZ) in these mice...
March 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28321600/post-6-ohda-lesion-exposure-to-stress-affects-neurotrophic-factor-expression-and-aggravates-motor-impairment
#16
Phumzile Nomfundo Ngema, Musa Vuyisile Mabandla
Chronic exposure to stress amplifies locomotor deficits and exacerbates dopamine neuron loss in an animal model for Parkinson's disease. The release of neurotrophic factors such as glial cell-line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) following neuronal injury attenuates exacerbated degeneration of these neurons. In this study, the neurotoxin 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle of male Sprague Dawley rats. A subset of these rats was subjected to post-lesion restraint stress after which the effect of exposure to stress on locomotor activity (forelimb akinesia test), neurotrophic factor (GDNF and NT-3) and corticosterone concentration was assessed...
March 20, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28316566/blockade-of-ryrs-in-the-er-attenuates-6-ohda-induced-calcium-overload-cellular-hypo-excitability-and-apoptosis-in-dopaminergic-neurons
#17
Lu Huang, Ying Xue, DaYun Feng, RuiXin Yang, Tiejian Nie, Gang Zhu, Kai Tao, GuoDong Gao, Qian Yang
Calcium (Ca(2+)) dyshomeostasis induced by endoplasmic reticulum (ER) stress is an important molecular mechanism of selective dopaminergic (DA) neuron loss in Parkinson's disease (PD). Inositol 1,4,5-triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), which are located on the ER surface, are the main endogenous Ca(2+) release channels and play crucial roles in regulating Ca(2+) homeostasis. However, the roles of these endogenous Ca(2+) release channels in PD and their effects on the function and survival of DA neurons remain unknown...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28315782/human-comt-over-expression-confers-a-heightened-susceptibility-to-dyskinesia-in-mice
#18
Oscar Solís, Jose-Rubén García-Montes, Patricia Garcia-Sanz, Antonio S Herranz, Maria-José Asensio, Gina Kang, Noboru Hiroi, Rosario Moratalla
Catechol-O-methyltransferase (COMT) degrades dopamine and its precursor l-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically with l-DOPA for two weeks. l-DOPA-induced dyskinesia was exacerbated in TG mice without altering l-DOPA motor efficacy as determined by contralateral rotations or motor coordination...
June 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#19
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28294337/copper-increases-the-ability-of-6-hydroxydopamine-to-generate-oxidative-stress-and-the-ability-of-ascorbate-and-glutathione-to-potentiate-this-effect-potential-implications-in-parkinson-s-disease
#20
Antón Cruces-Sande, Estefanía Méndez-Álvarez, Ramón Soto-Otero
Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6-Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals...
March 14, 2017: Journal of Neurochemistry
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