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https://www.readbyqxmd.com/read/28526609/effects-of-l-dopa-benserazide-co-treatment-on-colonic-excitatory-cholinergic-motility-and-enteric-inflammation-following-dopaminergic-nigrostriatal-neurodegeneration
#1
C Pellegrini, L Antonioli, R Colucci, E Tirotta, D Gentile, C Ippolito, C Segnani, G Levandis, S Cerri, R F Blandini, E Barocelli, V Ballabeni, N Bernardini, C Blandizzi, M Fornai
INTRODUCTION: The mainstay therapy for Parkinson's disease (PD) relies on L-3,4- dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. METHODS: Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the median forebrain bundle (MFB)...
May 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28511006/novel-focused-ultrasound-gene-therapy-approach-noninvasively-restores-dopaminergic-neuron-function-in-a-rat-parkinson-s-disease-model
#2
Brian P Mead, Namho Kim, G Wilson Miller, David Hodges, Panagiotis Mastorakos, Alexander L Klibanov, James W Mandell, Jay Hirsh, Jung Soo Suk, Justin Hanes, Richard J Price
Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy...
May 18, 2017: Nano Letters
https://www.readbyqxmd.com/read/28504195/fgf18-protects-against-6-hydroxydopamine-induced-nigrostriatal-damage-in-a-rat-model-of-parkinson-s-disease
#3
Xingzhi Guo, Tingting Liu, Diandian Zhao, Xiaofeng Wang, Dongmei Liu, Yang He, Chang Shan, Yingying Kong, Weiwei Hu, Bei Tao, Lihao Sun, Hongyan Zhao, Shengtian Li, Jianmin Liu
Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3β signaling pathway...
May 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28488766/brief-isoflurane-anesthesia-regulates-striatal-akt-gsk3%C3%AE-signaling-and-ameliorates-motor-deficits-in-a-rat-model-of-early-stage-parkinson-s-disease
#4
Juuso V Leikas, Samuel Kohtala, Wiebke Theilmann, Aaro J Jalkanen, Markus M Forsberg, Tomi Rantamäki
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder primarily affecting the nigrostriatal dopaminergic system. The link between heightened activity of glycogen synthase kinase 3β (GSK3β) and neurodegenerative processes has encouraged investigation into the potential disease modifying effects of novel GSK3β inhibitors in experimental models of PD. Therefore, the intriguing ability of several anesthetics to readily inhibit GSK3β within the cortex and hippocampus led us to investigate the effects of brief isoflurane anesthesia on striatal GSK3β signaling in naïve rats and in a rat model of early-stage PD...
May 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28479741/effect-of-naringenin-a-naturally-occurring-flavanone-against-pilocarpine-induced-status-epilepticus-and-oxidative-stress-in-mice
#5
Sheeba Shakeel, Muneeb U Rehman, Nahida Tabassum, Umar Amin, Manzoor Ur Rahman Mir
BACKGROUND: Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. It is a very common disease in which approximately 30% of patients do not respond favourably to treatment with anticonvulsants. Oxidative stress is associated with neuronal damage arising from epileptic seizures. The present study investigated the effects of naringenin in pilocarpine-induced epilepsy in mice. Naringenin, one of the most frequently occurring flavanone in citrus fruits, was evaluated for its shielding effect against the pilocarpine induced behavioural, oxidative and histopathological alterations in rodent model of epilepsy...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28469105/long-term-levodopa-treatment-accelerates-the-circadian-rhythm-dysfunction-in-a-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#6
Si-Yue Li, Ya-Li Wang, Wen-Wen Liu, Dong-Jun Lyu, Fen Wang, Cheng-Jie Mao, Ya-Ping Yang, Li-Fang Hu, Chun-Feng Liu
BACKGROUND: Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD. METHODS: The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days...
May 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28466266/prolonged-dysfunction-of-astrocytes-and-activation-of-microglia-accelerate-degeneration-of-dopaminergic-neurons-in-the-rat-substantia-nigra-and-block-compensation-of-early-motor-dysfunction-induced-by-6-ohda
#7
Katarzyna Kuter, Łukasz Olech, Urszula Głowacka
Progressive degeneration of dopaminergic neurons in the substantia nigra (SN) is the underlying cause of Parkinson's disease (PD). The disease in early stages is difficult to diagnose, because behavioral deficits are masked by compensatory processes. Astrocytic and microglial pathology precedes motor symptoms. Besides supportive functions of astrocytes in the brain, their role in PD is unrecognized. Prolonged dysfunction of astrocytes could increase the vulnerability of dopaminergic neurons and advance their degeneration during aging...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28455267/metabotropic-glutamate-receptor-5-mediates-the-suppressive-effect-of-6-ohda-induced-model-of-parkinson-s-disease-on-liver-cancer
#8
Shao-Song Xi, Xiao-Xu Bai, Li Gu, Li-Hui Bao, Hui-Min Yang, Wei An, Xiao-Min Wang, Hong Zhang
Numerous epidemiological studies suggested that there is a variable cancer risk in patients with Parkinson's disease (PD). However, the underlying mechanisms remain unclear. In the present study, the role of metabotropic glutamate receptor 5 (mGluR5) has been investigated in 6-hydroxydopamine (6-OHDA)-induced PD combined with liver cancer both in vitro and in vivo. We found that PD cellular model from 6-OHDA-lesioned MN9D cells suppressed the growth, migration, and invasion of Hepa1-6 cells via down-regulation of mGluR5-mediated ERK and Akt pathway...
April 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28439627/nigral-injection-of-a-proteasomal-inhibitor-lactacystin-induces-widespread-glial-cell-activation-and-shows-various-phenotypes-of-parkinson-s-disease-in-young-and-adult-mouse
#9
Mari H Savolainen, Katrina Albert, Mikko Airavaara, Timo T Myöhänen
Proteinaceous inclusions, called Lewy bodies, are used as a pathological hallmark for Parkinson's disease (PD). Lewy bodies contain insoluble α-synuclein (aSyn) and many other ubiquitinated proteins, suggesting a role for protein degradation system failure in the PD pathogenesis. Indeed, proteasomal dysfunction has been linked to PD but commonly used in vivo toxin models, such as 6-OHDA or MPTP, do not have a significant effect on the proteasomal system or protein aggregation. Therefore, we wanted to study the characteristics of a proteasomal inhibitor, lactacystin, as a PD model on young and adult mice...
April 24, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
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
#10
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 19, 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
#11
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 13, 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
#12
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
#13
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
#14
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
#15
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 6, 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
#16
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
#17
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
#18
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...
June 3, 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
#19
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
#20
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 blot 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
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