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https://www.readbyqxmd.com/read/28634107/chronic-pramipexole-treatment-induces-compulsive-behavior-in-rats-with-6-ohda-lesions-of-the-substantia-nigra-and-ventral-tegmental-area
#1
D Dardou, L Reyrolle, C Chassain, F Durif
Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions...
June 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28627694/investigation-of-the-neuroprotective-effects-of-a-novel-synthetic-compound-via-the-mitochondrial-pathway
#2
Di Wang, Shuang Hu, Junrong Zhang, Qiuyue Li, Xinyu Liu, Yu Li
The present study aimed to investigate the neuroprotective effect of a novel synthetic compound (5zou) on differentiated PC12 cells against 6‑hydroxydopamine (6‑OHDA) and L‑glutamic acid (L‑Glu) neurotoxin‑induced cell injury and the potential mechanisms involved. 5zou is a 2, 2‑disubstituted 1,2‑dihydropyridine. PC12 cells were treated with 6‑OHDA and L‑Glu to establish neurotoxic cell models. MTT assay, DCFH‑DA staining, Fluo‑4‑AM staining, JC‑1 staining and western blotting were used to determine the changes in cell viability, intracellular reactive oxygen species concentration, Ca2+ influx, mitochondrial membrane potential and the protein expressions of B‑cell lymphoma‑2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xL)...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28622392/therapeutic-efficacy-of-aav8-mediated-intrastriatal-delivery-of-human-cerebral-dopamine-neurotrophic-factor-in-6-ohda-induced-parkinsonian-rat-models-with-different-disease-progression
#3
Lizheng Wang, Zixuan Wang, Rui Zhu, Jinpeng Bi, Xinyao Feng, Wenmo Liu, Jiaxin Wu, Haihong Zhang, Hui Wu, Wei Kong, Bin Yu, Xianghui Yu
Parkinson's disease (PD) is a progressive and age-associated neurodegenerative disorder. Patients at different stages of the disease course have distinguished features, mainly in the number of dopaminergic neurons. Cerebral dopamine neurotrophic factor (CDNF) is a recently discovered neurotrophic factor, being deemed as a hopeful candidate for PD treatment. Here, we evaluated the efficacy of CDNF in protecting dopaminergic function using the 6-OHDA-induced PD rat model suffering from different levels of neuronal loss and the recombinant adeno-associated virus 8 (AAV8) as a carrier for the CDNF gene...
2017: PloS One
https://www.readbyqxmd.com/read/28620274/influence-of-estrogen-modulation-on-glia-activation-in-a-murine-model-of-parkinson-s-disease
#4
Francesca Siani, Rosaria Greco, Giovanna Levandis, Cristina Ghezzi, Francesca Daviddi, Chiara Demartini, Elisabetta Vegeto, Marie-Thérèse Fuzzati-Armentero, Fabio Blandini
Epidemiological data suggest a sexual dimorphism in Parkinson disease (PD), with women showing lower risk of developing PD. Vulnerability of the nigrostriatal pathway may be influenced by exposure to estrogenic stimulation throughout fertile life. To further address this issue, we analyzed the progression of nigrostriatal damage, microglia and astrocyte activation and microglia polarization triggered by intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in male, female and ovariectomized (OVX) mice, as well as in OVX mice supplemented with 17βestradiol (OVX+E)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28616718/effect-of-intrastriatal-6-ohda-lesions-on-extrastriatal-brain-structures-in-the-mouse
#5
Birte Becker, Melek Demirbas, Sonja Johann, Adib Zendedel, Cordian Beyer, Hans Clusmann, Stefan Jean-Pierre Haas, Andreas Wree, Sonny Kian Hwie Tan, Markus Kipp
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor and non-motor symptoms. The underlying pathology of non-motor symptoms is poorly understood. Discussed are pathological changes of extrastriatal brain structures. In this study, we characterized histopathological alterations of extrastriatal brain structures in the 6-hydroxydopamine (6-OHDA) PD animal model. Lesions were induced by unilateral stereotactic injections of 6-OHDA into the striatum or medial forebrain bundle of adult male mice...
June 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#6
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28592699/lower-affinity-of-isradipine-for-l-type-ca-2-channels-during-substantia-nigra-dopamine-neuron-like-activity-implications-for-neuroprotection-in-parkinson-s-disease
#7
Nadine J Ortner, Gabriella Bock, Antonios Dougalis, Maria Kharitonova, Johanna Duda, Simon Hess, Petronel Tuluc, Thomas Pomberger, Nadia Stefanova, Florian Pitterl, Thomas Ciossek, Herbert Oberacher, Henning J Draheim, Peter Kloppenburg, Birgit Liss, Jörg Striessnig
Ca(2+)-influx through L-type Ca(2+)-channels (LTCCs) is associated with activity-related stressful oscillations of Ca(2+)-levels within dopaminergic (DA) neurons in the substantia nigra (SN), which may contribute to their selective degeneration in Parkinson's disease (PD). LTCC blockers were neuroprotective in mouse neurotoxin models of PD and isradipine is currently undergoing testing in a phase-III clinical trial in early PD. We report no evidence for neuroprotection by in vivo pretreatment with therapeutically relevant isradipine plasma levels, or Cav1...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28583881/altered-adenosine-2a-and-dopamine-d2-receptor-availability-in-the-6-hydroxydopamine-treated-rats-with-and-without-levodopa-induced-dyskinesia
#8
X Zhou, J Doorduin, P H Elsinga, R A J O Dierckx, E F J de Vries, C Casteels
Several lines of evidence imply alterations in adenosine signaling in Parkinson's disease (PD). Here, we investigated cerebral changes in adenosine 2A receptor (A2AR) availability in 6-hydroxydopamine (6-OHDA)-lesioned rats with and without levodopa-induced dyskinesia (LID) using positron-emission tomography (PET) with [(11)C]preladenant. In parallel dopamine type 2 receptor (D2R) imaging with [(11)C]raclopride PET and behavioral tests for motor and cognitive function were performed. METHODS: Parametric A2AR and D2R binding potential (BPND) images were reconstructed using reference tissue models with midbrain and cerebellum as reference tissue, respectively...
June 2, 2017: NeuroImage
https://www.readbyqxmd.com/read/28579395/cryopreservation-maintains-functionality-of-human-ipsc-dopamine-neurons-and-rescues-parkinsonian-phenotypes-in%C3%A2-vivo
#9
Dustin R Wakeman, Benjamin M Hiller, David J Marmion, Christopher W McMahon, Grant T Corbett, Kile P Mangan, Junyi Ma, Lauren E Little, Zhong Xie, Tamara Perez-Rosello, Jaime N Guzman, D James Surmeier, Jeffrey H Kordower
A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage...
May 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28577987/alcar-promote-adult-hippocampal-neurogenesis-by-regulating-cell-survival-and-cell-death-related-signals-in-rat-model-of-parkinson-s-disease-like-phenotypes
#10
Sonu Singh, Akanksha Mishra, Sandeep Kumar Mishra, Shubha Shukla
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway that leading to progressive motor and nonmotor symptoms. The formation of newborn neurons in the adult hippocampus is affected by many factors such as anxiety, depression and impairment in learning and memory that are commonly observed nonmotor symptoms in PD, indicating the role of adult neurogenesis in PD pathophysiology. Acetyl-l-carnitine (ALCAR), regulate mitochondrial metabolism and has been reported to improve cognitive functions in different neurodegenerative disorders through an unknown mechanism...
May 31, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28569795/cystatin-c-as-a-potential-therapeutic-mediator-against-parkinson-s-disease-via-vegf-induced-angiogenesis-and-enhanced-neuronal-autophagy-in-neurovascular-units
#11
Jing Zou, Zhaoyu Chen, Xiaobo Wei, Zhigang Chen, Yongmei Fu, Xiaoyan Yang, Dan Chen, Rui Wang, Peter Jenner, Jia-Hong Lu, Min Li, Zhuohua Zhang, Beisha Tang, Kunlin Jin, Qing Wang
Cystatin C (CYS C, Cst3) is an endogenous cysteine protease inhibitor that plays neuroprotective roles in neurodegenerative diseases. We aimed to explore the association of CYS C with Parkinson's disease (PD) models and investigate its involvement in the role of neurovascular units (NVUs) in PD neuro-pathogenesis. We used A53T α-synuclein (SNCA) transgenic mice and 6-hydroxydopamine-lesioned DAergic PC12 cells as experimental PD models to investigate the mechanisms behind this association. The injections of CYS C were administered to the right substantia nigra (SN) of A53T SNCA transgenic mice to measure the effects of CYS C in transgenic A53T SNCA mice...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28557659/geminin-participates-in-differentiation-decisions-of-adult-neural-stem-cells-transplanted-in-the-hemiparkinsonian-mouse-brain
#12
Ioanna Taouki, Eve Tasiudi, Maria-Eleni Lalioti, Christina Kyrousi, Eleni Skavatsou, Konstantina Kaplani, Zoi Lygerou, Elias D Kouvelas, Adamantia Mitsacos, Panagiotis Giompres, Stavros Taraviras
Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. Here, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6 OHDA hemiparkinsonian mouse model...
May 30, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28554717/phenylalanine-derivatives-with-modulating-effects-on-human-%C3%AE-1-glycine-receptors-and-anticonvulsant-activity-in-strychnine-induced-seizure-model-in-male-adult-rats
#13
Bassem Sadek, Murat Oz, Syed M Nurulain, Petrilla Jayaprakash, Gniewomir Latacz, Katarzyna Kieć-Kononowicz, Ewa Szymańska
The critical role of α1-glycine receptor (α1-GLYRs) in pathological conditions such as epilepsy is well known. In the present study, structure-activity relations for a series of phenylalanine derivatives carrying selected hydrogen bond acceptors were investigated on the functional properties of human α1-GLYR expressed in Xenopus oocytes. The results indicate that one particular substitution position appeared to be of special importance for control of ligand activity. Among tested ligands (1-8), the biphenyl derivative (2) provided the most promising antagonistic effect on α1-GLYRs, while its phenylbenzyl analogue (5) exhibited the highest potentiation effect...
May 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28553166/recombinant-aav8-mediated-intrastriatal-gene-delivery-of-cdnf-protects-rats-against-methamphetamine-neurotoxicity
#14
Lizheng Wang, Zixuan Wang, Xiaoyu Xu, Rui Zhu, Jinpeng Bi, Wenmo Liu, Xinyao Feng, Hui Wu, Haihong Zhang, Jiaxin Wu, Wei Kong, Bin Yu, Xianghui Yu
Methamphetamine (METH) exerts significant neurotoxicity in experimental animals and humans when taken at high doses or abused chronically. Long-term abusers have decreased dopamine levels, and they are more likely to develop Parkinson's disease (PD). To date, few medications are available to treat the METH-induced damage of neurons. Glial cell line-derived neurotrophic factor (GDNF) has been previously shown to reduce the dopamine-depleting effects of neurotoxic doses of METH. However, the effect of cerebral dopamine neurotrophic factor (CDNF), which has been reported to be more specific and efficient than GDNF in protecting dopaminergic neurons against 6-OHDA toxicity, in attenuating METH neurotoxicity has not been determined...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28549887/fluvoxamine-maleate-effects-on-dopamine-signaling-in-the-prefrontal-cortex-of-stressed-parkinsonian-rats-implications-for-learning-and-memory
#15
Ernest Dallé, Willie M U Daniels, Musa V Mabandla
Parkinson's disease (PD) is also associated with cognitive impairment and reduced extrinsic supply of dopamine (DA) to the prefrontal cortex (PFC). In the present study, we looked at whether exposure to early life stress reduces DA and serotonin (5-HT) concentration in the PFC thus leading to enhanced cognitive impairment in a Parkinsonian rat model. Maternal separation was the stressor used to develop an animal model for early life stress that has chronic effects on brain and behavior. Sprague-Dawley rats were treated with the antidepressant Fluvoxamine maleate (FM) prior to a unilateral 6-hydroxydopamine (6-OHDA) lesion to model motor deficits in rats...
May 24, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28543594/the-neuroprotective-role-of-mir-124-3p-in-a-6-hydroxydopamine-induced-cell-model-of-parkinson-s-disease-via-the-regulation-of-anax5
#16
Rui-Fang Dong, Bing Zhang, Li-Wen Tai, Hong-Mei Liu, Fang-Kun Shi, Ning-Ning Liu
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Several pathogenetic factors have been involved in the onset and progression of PD, including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Ample evidence indicates that miRNAs could regulate post-transcriptional gene expression and neuronal disease. In this study, we evaluated the effects and mechanism of miR-124-3p on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and SH-SY5Y cells...
May 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28539659/involvement-of-the-bed-nucleus-of-the-stria-terminalis-in-l-dopa-induced-dyskinesia
#17
Matthieu F Bastide, Christelle Glangetas, Evelyne Doudnikoff, Qin Li, Mathieu Bourdenx, Pierre-Olivier Fernagut, Éric C Dumont, François Georges, Erwan Bézard
A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson's disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536975/a-new-hope-for-a-devastating-disease-hydrogen-sulfide-in-parkinson-s-disease
#18
REVIEW
Xu Cao, Lei Cao, Lei Ding, Jin-Song Bian
Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, H2S is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, H2S has been found to induce the formation of long-term potential in neuronal cells by augmenting the activity of N-methyl-D-aspartate (NMDA) receptor. Likewise, it also actively takes part in the regulation of intracellular Ca(2+) and pH homeostasis in both neuronal cells and glia cells...
May 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28536652/mesencephalic-astrocyte-derived-neurotrophic-factor-reduces-cell-apoptosis-via-upregulating-hsp70-in-shsy-5y-cells
#19
Hui Sun, Ming Jiang, Xing Fu, Qiong Cai, Jingxing Zhang, Yanxin Yin, Jia Guo, Lihua Yu, Yun Jiang, Yigang Liu, Liang Feng, Zhiyu Nie, Jianmin Fang, Lingjing Jin
BACKGROUND: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress (ER stress). HSP70 family, a chaperon like heat shock protein family, was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells. However, the ER stress relative transcriptome, in MANF signaling cascades is still investigated. The involvement of HSP70, a 70kd member of HSP70 family, need further to be verified...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28534853/the-1-tosylpentan-3-one-protects-against-6-hydroxydopamine-induced-neurotoxicity
#20
Chien-Jen Kao, Wu-Fu Chen, Bo-Lin Guo, Chien-Wei Feng, Han-Chun Hung, Wen-Ya Yang, Chun-Sung Sung, Kuan-Hao Tsui, Hsin Chu, Nan-Fu Chen, Zhi-Hong Wen
Previous studies have demonstrated that the marine compound austrasulfone, isolated from the soft coral Cladiella australis, exerts a neuroprotective effect. The intermediate product in the synthesis of austrasulfone, dihydroaustrasulfone alcohol, attenuates several inflammatory responses. The present study uses in vitro and in vivo methods to investigate the neuroprotective effect of dihydroaustrasulfone alcohol-modified 1-tosylpentan-3-one (1T3O). Results from in vitro experiments show that 1T3O effectively inhibits 6-hydroxydopamine-induced (6-OHDA-induced) activation of both p38 mitogen-activated protein kinase (MAPK) and caspase-3 in SH-SY5Y cells; and enhances nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling...
May 19, 2017: International Journal of Molecular Sciences
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