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https://www.readbyqxmd.com/read/28537985/neuroimaging-in-parkinson-s-disease-focus-on-substantia-nigra-and-nigro-striatal-projection
#1
Daniela Frosini, Mirco Cosottini, Duccio Volterrani, Roberto Ceravolo
PURPOSE OF REVIEW: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. RECENT FINDINGS: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation...
May 22, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#2
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28516282/region-specific-iron-measured-by-mri-as-a-biomarker-for-parkinson-s-disease
#3
REVIEW
Xiaojun Guan, Xiaojun Xu, Minming Zhang
The identification of sensitive and specific biomarkers for Parkinson's disease (PD) poses an important clinical challenge. A potential biomarker for early diagnosis and disease monitoring of PD is region-specific iron. Iron accumulation in the substantia nigra pars compacta is considered a main characteristic of PD. However, questions remain, such as the relationship between nigral iron and clinical indices of PD (motor impairment or disease duration). Further, previous studies have suggested the influence of iron on other nuclei...
May 17, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28507529/parkinson-disease-an-evolutionary-perspective
#4
Pedro J Garcia-Ruiz, Alberto J Espay
There are two central premises to this evolutionary view of Parkinson disease (PD). First, PD is a specific human disease. Second, the prevalence of PD has increased over the course of human history. Several lines of evidence may explain why PD appears to be restricted to the human species. The major manifestations of PD are the consequence of degeneration in the dopamine-synthesizing neurons of the mesostriatal neuronal pathway. It is of note the enormous expansion of the human dopamine mesencephalic neurons onto the striatum compared with other mammals...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28493825/repetitive-transcranial-magnetic-stimulation-for-treatment-of-lactacystin-induced-parkinsonian-rat-model
#5
Maowen Ba, Guozhao Ma, Chao Ren, Xuwen Sun, Min Kong
The dysfunction of ubiquitin-proteasome system is an important pathogenesis in the neurodegenerative process of Parkinson's disease. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and potential method in treating Parkinson's disease. To investigate whether rTMS has neuroprotective effects in parkinsonian rat model induced by ubiquitin-proteasome system impairment, we gave rTMS daily for 4 weeks to proteasome inhibitor, lactacystin-induced parkinsonian rat model. Rotational behavior test demonstrated that rTMS obviously reduced apomorphine-induced turning number in parkinsonian rats...
April 20, 2017: Oncotarget
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
#6
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/28479587/structure-distribution-and-genetic-profile-of-%C3%AE-synuclein-and-their-potential-clinical-application-in-parkinson-s-disease
#7
Xiaoli Si, Jiali Pu, Baorong Zhang
Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy...
May 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28471847/neuroprotective-effect-of-resveratrol-on-rotenone-treated-c57bl-6-mice
#8
Xiaofei Zhao, Jun Wang, Song Hu, Renping Wang, Yongjun Mao, Junxia Xie
The aim of the present study was to investigate whether resveratrol could reduce nigral iron levels to prevent the degeneration of dopaminergic neurons in the substantia nigra (SN) of C57BL/6 mice induced by rotenone. Parkinson's disease (PD) is an age-related neurodegenerative disorder; elevated iron levels in the SN participate in neuronal death in PD. Resveratrol is a kind of polyphenolic compounds and possess antioxidant, anticancer, and anti-inflammatory biological functions. Although many research groups have investigated the neuroprotective effects of resveratrol against PD, the precise mechanisms underlying its beneficial effects on dopaminergic neuron are poorly defined...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28450223/gper-activation-is-effective-in-protecting-against-inflammation-induced-nigral-dopaminergic-loss-and-motor-function-impairment
#9
Julieta Mendes-Oliveira, Filipa Lopes Campos, Rita Alexandra Videira, Graça Baltazar
Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects...
April 24, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28446566/induction-of-adaptive-immunity-leads-to-nigrostriatal-disease-progression-in-mptp-mouse-model-of-parkinson-s-disease
#10
Goutam Chandra, Avik Roy, Suresh B Rangasamy, Kalipada Pahan
Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most widely used animal model for Parkinson's disease (PD), it is known that nigrostriatal pathologies do not persist in the acute MPTP mouse model. This study highlights the importance of adaptive immunity in driving persistent and progressive disease in acute MPTP-intoxicated mice. Although marked infiltration of T cells into the nigra was found on 1 d of MPTP insult, T cell infiltration decreased afterward, becoming normal on 30 d of insult...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#11
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/28408878/reward-based-motor-adaptation-mediated-by-basal-ganglia
#12
Taegyo Kim, Khaldoun C Hamade, Dmitry Todorov, William H Barnett, Robert A Capps, Elizaveta M Latash, Sergey N Markin, Ilya A Rybak, Yaroslav I Molkov
It is widely accepted that the basal ganglia (BG) play a key role in action selection and reinforcement learning. However, despite considerable number of studies, the BG architecture and function are not completely understood. Action selection and reinforcement learning are facilitated by the activity of dopaminergic neurons, which encode reward prediction errors when reward outcomes are higher or lower than expected. The BG are thought to select proper motor responses by gating appropriate actions, and suppressing inappropriate ones...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#13
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
#14
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
#15
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...
May 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
#16
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
#17
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
#18
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...
April 15, 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
#19
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...
April 11, 2017: Neurology
https://www.readbyqxmd.com/read/28281653/nix-restores-mitophagy-and-mitochondrial-function-to-protect-against-pink1-parkin-related-parkinson-s-disease
#20
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
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