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https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#1
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28320442/analysis-of-monocyte-infiltration-in-mptp-mice-reveals-that-microglial-cx3cr1-protects-against-neurotoxic-over-induction-of-monocyte-attracting-ccl2-by-astrocytes
#2
Vincent R Parillaud, Guillaume Lornet, Yann Monnet, Anne-Laure Privat, Andrei T Haddad, Vanessa Brochard, Amaury Bekaert, Camille Baudesson de Chanville, Etienne C Hirsch, Christophe Combadière, Stéphane Hunot, Christian S Lobsiger
BACKGROUND: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2(+) monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death...
March 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28296268/feasibility-and-efficacy-of-intra-arterial-administration-of-mesenchymal-stem-cells-in-an-animal-model-of-double-toxin-induced-multiple-system-atrophy
#3
Ha Na Kim, Dong Yeol Kim, Se Hee Oh, Hyung Sook Kim, Kyung Suk Kim, Phil Hyu Lee
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and autonomic nervous system. Because no drug treatment consistently benefits MSA patients, neuroprotective strategy using mesenchymal stem cells (MSCs) has a lot of concern for the management of MSA. In this study, we investigated the safety and efficacy of intra-arterial administration of MSCs via internal carotid artery (ICA) in an animal model of MSA. The study was composed of feasibility test using a ×10 and ×50 of a standard dose of MSCs (4 × 10(7) MSCs) and efficacy test using a ×0...
March 13, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28292328/age-dependent-dopamine-transporter-dysfunction-and-serine129-phospho-%C3%AE-synuclein-overload-in-g2019s-lrrk2-mice
#4
Francesco Longo, Daniela Mercatelli, Salvatore Novello, Ludovico Arcuri, Alberto Brugnoli, Fabrizio Vincenzi, Isabella Russo, Giulia Berti, Omar S Mabrouk, Robert T Kennedy, Derya R Shimshek, Katia Varani, Luigi Bubacco, Elisa Greggio, Michele Morari
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease. Here, we investigated whether the G2019S LRRK2 mutation causes morphological and/or functional changes at nigro-striatal dopamine neurons. Density of striatal dopaminergic terminals, nigral cell counts, tyrosine hydroxylase protein levels as well as exocytotic dopamine release measured in striatal synaptosomes, or striatal extracellular dopamine levels monitored by in vivo microdialysis were similar between ≥12-month-old G2019S knock-in mice and wild-type controls...
March 14, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28285346/complex-changes-in-the-innate-and-adaptive-immunity-accompany-progressive-degeneration-of-the-nigrostriatal-pathway-induced-by-intrastriatal-injection-of-6-hydroxydopamine-in-the-rat
#5
Giulia Ambrosi, Natasa Kustrimovic, Francesca Siani, Emanuela Rasini, Silvia Cerri, Cristina Ghezzi, Giuseppe Dicorato, Sofia Caputo, Franca Marino, Marco Cosentino, Fabio Blandini
We investigated changes in innate and adaptive immunity paralleling the progressive nigrostriatal damage occurring in a neurotoxic model of Parkinson's disease (PD) based on unilateral infusion of 6-hydroxydopamine (6-OHDA) into the rat striatum. A time-course analysis was conducted to assess changes in morphology (activation) and cell density of microglia and astrocytes, microglia polarization (M1 vs. M2 phenotype), lymphocyte infiltration in the lesioned substantia nigra pars compacta (SNc), and modifications of CD8+ and subsets of CD4+ T cell in peripheral blood accompanying nigrostriatal degeneration...
March 11, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28284752/troxerutin-exerts-neuroprotection-in-6-hydroxydopamine-lesion-rat-model-of-parkinson-s-disease-possible-involvement-of-pi3k-er%C3%AE-signaling
#6
Tourandokht Baluchnejadmojarad, Nida Jamali-Raeufy, Sedigheh Zabihnejad, Nafiseh Rabiee, Mehrdad Roghani
Parkinson's disease (PD) is a neurodegenerative disease with progressive loss of mesencephalic dopaminergic neurons of the substantia nigra and with multiple incapacitating motor and non-motor symptoms. Troxerutin is a natural bioflavonoid with nephro- and hepato-protective, antioxidant, and anti-inflammatory properties. In this study, we evaluated its possible neuroprotective effect in 6-hydroxydopamine (6-OHDA) rat model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with troxerutin at a dose of 150mg/kg/day for 1 week...
March 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28283599/dopamine-transporter-imaging-does-not-predict-the-number-of-nigral-neurons-in-parkinson-disease
#7
Laura Saari, Katri Kivinen, Maria Gardberg, Juho Joutsa, Tommi Noponen, Valtteri Kaasinen
OBJECTIVE: To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD). METHODS: Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses...
March 10, 2017: Neurology
https://www.readbyqxmd.com/read/28281653/nix-restores-mitophagy-and-mitochondrial-function-to-protect-against-pink1-parkin-related-parkinson-s-disease
#8
Brianada Koentjoro, Jin-Sung Park, Carolyn M Sue
Therapeutic targets are needed to develop neuroprotective treatments for Parkinson's disease (PD). Mitophagy, the selective autophagic elimination of dysfunctional mitochondria, is essential for the maintenance of mitochondrial integrity and is predominantly regulated by the PINK1/Parkin-mediated pathway. Loss of function mutations in Parkin and PINK1 cause an accumulation of dysfunctional mitochondria, leading to nigral neurodegeneration and early-onset PD with a high penetrance rate. We previously identified an asymptomatic homozygous Parkin mutation carrier who had not developed PD by her eighth decade despite the loss of functional Parkin...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28279753/partial-lesion-of-dopamine-neurons-of-rat-substantia-nigra-impairs-conditioned-place-aversion-but-spares-conditioned-place-preference
#9
Bernardo F C Lima, Daniele C Ramos, Janaína K Barbiero, Laura Pulido, Peter Redgrave, Donita L Robinson, Alexander Gómez-A, Claudio Da Cunha
Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of thedopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning.Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3 μg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200 μg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28273852/caloric-restriction-protects-against-lactacystin-induced-degeneration-of-dopamine-neurons-independent-of-the-ghrelin-receptor
#10
Jessica Coppens, Eduard Bentea, Jacqueline A Bayliss, Thomas Demuyser, Laura Walrave, Giulia Albertini, Joeri Van Liefferinge, Lauren Deneyer, Najat Aourz, Ann Van Eeckhaut, Jeanelle Portelli, Zane B Andrews, Ann Massie, Dimitri De Bundel, Ilse Smolders
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by a loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Caloric restriction (CR) has been shown to exert ghrelin-dependent neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-based animal model for PD. We here investigated whether CR is neuroprotective in the lactacystin (LAC) mouse model for PD, in which proteasome disruption leads to the destruction of the DA neurons of the SNc, and whether this effect is mediated via the ghrelin receptor...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28258522/sitagliptin-and-liraglutide-reversed-nigrostriatal-degeneration-of-rodent-brain-in-rotenone-induced-parkinson-s-disease
#11
Ghada A Badawi, Mai A Abd El Fattah, Hala F Zaki, Moushira I El Sayed
The present study investigated the possible relationship between pro-inflammatory cytokines and programmed nigral neuronal death in rotenone model of Parkinson's disease (PD). Sitagliptin and liraglutide efficacy to inhibit the inflammatory-apoptotic degenerative process were investigated, too. The experimental PD were induced in male albino rats by ten subcutaneously injections of rotenone (3 mg/kg/day, s.c). All treatment drugs were administered for 16 days after induction of Parkinson rat's model. Sitagliptin and liraglutide were administered in three different dose levels (10-20-30 mg/kg, p...
March 4, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28256089/striatal-activation-by-optogenetics-induces-dyskinesias-in-the-6-hydroxydopamine-rat-model-of-parkinson-disease
#12
Ledia F Hernández, Ivan Castela, Irene Ruiz-DeDiego, Jose A Obeso, Rosario Moratalla
BACKGROUND: Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood. METHODS: We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle...
March 3, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28249117/anti-inflammatory-and-neuroprotective-activity-of-boswellic-acids-in-rotenone-parkinsonian-rats
#13
Angie Ameen, Amany Elkazaz, Hala M F A Mohammad, Bassant Mohamed Barakat
There is evidence that inflammation and oxidative stress contribute to neurodegenerative changes observed in Parkinson's disease (PD). Unfortunately, there is a lack of curative treatments for this debilitating movement disorder. Boswellic acids (BAs) are pentacyclic triterpene molecules of plant origin and have been utilized for treating many inflammatory conditions. The current study was conducted to explore the role of BAs in protection from rotenone-induced experimental Parkinsonism. Twenty four rats were assigned as vehicle group, rotenone control group: rats received rotenone (1 mg/kg) every 48...
March 1, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28245954/ceftriaxone-attenuates-glutamate-mediated-neuro-inflammation-and-restores-bdnf-in-mptp-model-of-parkinson-s-disease-in-rats
#14
Baninder Kaur, Atish Prakash
The present study is designed to investigate the role of glutamate transporter in neuroprotection of ceftriaxone against MPTP induced PD animal model. Young male Wistar rats were subjected to intra-nigral administration of MPTP for the induction of Parkinson's disease. Glutamate modulators like ceftriaxone (CFX), Memantine (MEM) and Dihydrokainate (DHK) were administered to MPTP-lesioned rats. Different behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical parameters were measured...
February 10, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28243821/the-impact-of-short-and-long-term-exercise-on-the-expression-of-arc-and-ampars-during-evolution-of-the-6-hydroxy-dopamine-animal-model-of-parkinson-s-disease
#15
P C Garcia, C C Real, L R Britto
The loss of nigral dopaminergic neurons typical in Parkinson's disease (PD) is responsible for hyperexcitability of medium spiny neurons resulting in abnormal corticostriatal glutamatergic synaptic drive. Considering the neuroprotective effect of exercise, the changes promoted by exercise on AMPA-type glutamate receptors (AMPARs), and the role of activity-regulated cytoskeleton-associated protein (Arc) in the AMPARs trafficking, we studied the impact of short and long-term treadmill exercise during evolution of the unilateral 6-hydroxy-dopamine (6-OHDA) animal model of PD...
February 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28240402/in-vivo-detection-of-lateral-ventral-tier-nigral-degeneration-in-parkinson-s-disease
#16
Daniel E Huddleston, Jason Langley, Jan Sedlacik, Kai Boelmans, Stewart A Factor, Xiaoping P Hu
The objective of this study was to measure neuromelanin-sensitive MRI contrast changes in the lateral-ventral tier of substantia nigra pars compacta in Parkinson's disease (PD). Histopathological studies of PD have demonstrated both massive loss of melanized dopamine neurons and iron accumulation in the substantia nigra pars compacta. Neurodegeneration is most profound in the lateral-ventral tier of this structure. We have previously shown in both healthy controls and individuals with PD that neuromelanin-sensitive MRI and iron-sensitive MRI contrast regions in substantia nigra overlap...
February 27, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28219741/regulation-of-human-gdnf-gene-expression-in-nigral-dopaminergic-neurons-using-a-new-doxycycline-regulated-nts-polyplex-nanoparticle-system
#17
Armando J Espadas-Alvarez, Michael J Bannon, Carlos E Orozco-Barrios, Lourdes Escobedo-Sanchez, Jose Ayala-Davila, David Reyes-Corona, Guadalupe Soto-Rodriguez, Vicente Escamilla-Rivera, Andrea De Vizcaya-Ruiz, M Eugenia Gutierrez-Castillo, America Padilla-Viveros, Daniel Martinez-Fong
The human glial-cell derived neurotrophic factor (hGDNF) gene transfer by neurotensin (NTS)-polyplex nanoparticles functionally restores the dopamine nigrostriatal system in experimental Parkinson's disease models. However, high levels of sustained expression of GDNF eventually can cause harmful effects. Herein, we report an improved NTS-polyplex nanoparticle system that enables regulation of hGDNF expression within dopaminergic neurons. We constructed NTS-polyplex nanoparticles containing a single bifunctional plasmid that codes for the reverse tetracycline-controlled transactivator advanced (rtTA-Adv) under the control of NBRE3x promoter, and for hGDNF under the control of tetracycline-response element (TRE)...
February 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28212832/motor-dysfunction-and-alterations-in-glutathione-concentration-cholinesterase-activity-and-bdnf-expression-in-substantia-nigra-pars-compacta-in-rats-with-pedunculopontine-lesion
#18
Lisette Blanco-Lezcano, Javier Jimenez-Martin, Mei-Li Díaz-Hung, Esteban Alberti-Amador, Maylin Wong-Guerra, Ma Elena González-Fraguela, Bárbara Estupiñán-Díaz, Teresa Serrano-Sánchez, Liliana Francis-Turner, Susana Delgado-Ocaña, Yanier Núñez-Figueredo, Yamilé Vega-Hurtado, Isabel Fernández-Jiménez
Pedunculopontine nucleus (PPN) has been considered a critically important region in the regulation of some of the physiological functions that fail during the progression of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN [through the injection of N-methyl-d-aspartate (NMDA) solution (concentration: 0.1M; volume: 0.5µL)] in motor execution and gait disorders and the changes in cellular and molecular indicators in rat nigral tissue were evaluated. The motor execution was assessed using the beam test (BT) and the gait disorders by footprint test...
February 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28199883/acetyl-l-carnitine-protects-dopaminergic-nigrostriatal-pathway-in-6-hydroxydopamine-induced-model-of-parkinson-s-disease-in-the-rat
#19
Siamak Afshin-Majd, Keyhan Bashiri, Zahra Kiasalari, Tourandokht Baluchnejadmojarad, Reza Sedaghat, Mehrdad Roghani
Parkinson's disease (PD) is a movement disorder and the second most common neurodegenerative disease worldwide in which nigrostriatal dopaminergic neurons within substantia nigra pars compacta (SNC) are lost, with clinical motor and non-motor symptoms including bradykinesia, resting tremor, rigidity, stooping posture and cognitive deficits. This study was undertaken to evaluate the neuroprotective potential of acetyl-l-carnitine (ALC) against unilateral striatal 6-hydroxydopamine (6-OHDA)-induced model of PD and to explore some involved mechanisms...
February 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28196514/defining-the-contribution-of-neuroinflammation-to-parkinson-s-disease-in-humanized-immune-system-mice
#20
Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R Scherzer, Colin Kelly Combs
BACKGROUND: Reactive microglia have been associated with the histological changes that occur in Parkinson's disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson's disease have not been fully defined...
February 14, 2017: Molecular Neurodegeneration
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