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https://www.readbyqxmd.com/read/29218504/temporal-spatial-profiling-of-pedunculopontine-galanin-cholinergic-neurons-in-the-lactacystin-rat-model-of-parkinson-s-disease
#1
Joanna L Elson, Rafael Kochaj, Richard Reynolds, Ilse S Pienaar
Parkinson's disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, while being upregulated in degenerating brain regions associated with cognitive decline...
December 7, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29217687/role-of-the-axon-initial-segment-in-the-control-of-spontaneous-frequency-of-nigral-dopaminergic-neurons-in-vivo
#2
Rodrigo C Meza, Luciana López-Jury, Carmen C Canavier, Pablo Henny
The spontaneous tonic discharge activity of nigral dopamine neurons plays a fundamental role in dopaminergic signaling. To investigate the role of neuronal morphology and architecture with respect to spontaneous activity in this population, we visualized the 3D structure of the axon initial segment (AIS) along with the entire somatodendritic domain of adult male mouse dopaminergic neurons, previously recorded in vivo We observed a positive correlation of the firing rate with both proximity and size of the AIS...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217686/synaptic-regulator-%C3%AE-synuclein-in-dopaminergic-fibers-is-essentially-required-for-the-maintenance-of-subependymal-neural-stem-cells
#3
Ana Perez-Villalba, Mª Salomé Sirerol-Piquer, Germán Belenguer, Raúl Soriano-Cantón, Ana Belén Muñoz-Manchado, Javier Villadiego, Diana Alarcón-Arís, Federico N Soria, Benjamin Dehay, Erwan Bezard, Miquel Vila, Analía Bortolozzi, Juan José Toledo-Aral, Francisco Pérez-Sánchez, Isabel Fariñas
Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to MPTP or intranigral inoculation of aggregated toxic α-SYN...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29201000/striatal-g%C3%AE-olf-camp-signal-dependent-mechanism-to-generate-levodopa-induced-dyskinesia-in-parkinson-s-disease
#4
Satoshi Goto
The motor symptoms of Parkinson's disease (PD) result from striatal dopamine (DA) deficiency due to a progressive degeneration of nigral dopaminergic cells. Although DA replacement therapy is the mainstay to treat parkinsonian symptoms, a long-term daily administration of levodopa often develops levodopa-induced dyskinesia (LID). LID is closely linked to the dysregulation of cyclic adenosine monophosphate (cAMP) signaling cascades in the medium spiny neurons (MSNs), the principal neurons of the striatum, which are roughly halved with striatonigral MSNs by striatopallidal MSNs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29188990/reactive-dopamine-leads-to-triple-trouble-in-nigral-neurons
#5
Markus Riessland, Benjamin Kolisnyk, Paul Greengard
No abstract text is available yet for this article.
November 30, 2017: Biochemistry
https://www.readbyqxmd.com/read/29180403/sumoylation-and-ubiquitination-reciprocally-regulate-%C3%AE-synuclein-degradation-and-pathological-aggregation
#6
Ruth Rott, Raymonde Szargel, Vered Shani, Haya Hamza, Mor Savyon, Fatimah Abd Elghani, Rina Bandopadhyay, Simone Engelender
α-Synuclein accumulation is a pathological hallmark of Parkinson's disease (PD). Ubiquitinated α-synuclein is targeted to proteasomal or lysosomal degradation. Here, we identify SUMOylation as a major mechanism that counteracts ubiquitination by different E3 ubiquitin ligases and regulates α-synuclein degradation. We report that PIAS2 promotes SUMOylation of α-synuclein, leading to a decrease in α-synuclein ubiquitination by SIAH and Nedd4 ubiquitin ligases, and causing its accumulation and aggregation into inclusions...
November 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29176896/aging-related-limit-of-exercise-efficacy-on-motor-decline
#7
Jennifer C Arnold, Mark A Cantu, Ella A Kasanga, Vicki A Nejtek, Evan V Papa, Nicoleta Bugnariu, Michael F Salvatore
Identifying lifestyle strategies and allied neurobiological mechanisms that reduce aging-related motor impairment is imperative, given the accelerating number of retirees and increased life expectancy. A physically active lifestyle prior to old age can reduce risk of debilitating motor decline. However, if exercise is initiated after motor decline has begun in the lifespan, it is unknown if aging itself may impose a limit on exercise efficacy to decelerate further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF) rats, locomotor activity begins to decrease in middle age (12-18 months)...
2017: PloS One
https://www.readbyqxmd.com/read/29174294/the-kv7-kcnq-channel-blocker-xe991-protects-nigral-dopaminergic-neurons-in-the-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#8
Haixia Liu, Lu Jia, Xiaoyan Chen, Limin Shi, Junxia Xie
The excitability of dopaminergic neurons in the substantia nigra pars compacta (SNc) that supply the striatum with dopamine (DA) determines the function of the nigrostriatal system for motor coordination. We previously showed that 4-pyridinylmethyl-9(10H)-anthracenone (XE991), a specific blocker of Kv7/KCNQ channels, enhanced the excitability of nigral DA neurons and resulted in attenuation of haloperidol-induced catalepsy in a Parkinson's disease (PD) rat model. However, whether XE991 exhibits neuroprotective effects towards DA neuron degeneration remains unknown...
November 21, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29162435/pioglitazone-reduces-mortality-prevents-depressive-like-behavior-and-impacts-hippocampal-neurogenesis-in-the-6-ohda-model-of-parkinson-s-disease-in-rats
#9
Jéssica Mendes Bonato, Taysa Bervian Bassani, Humberto Milani, Maria Aparecida Vital, Rúbia Maria Weffort de Oliveira
Deficiencies in adult hippocampal neurogenesis have been suggested to be a possible pathophysiological mechanism that underlies depressive symptoms that are often observed in patients with Parkinson's disease (PD). Pioglitazone, a selective peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, has been shown to exert antiinflammatory and antidepressant effects and modulate neural plasticity in several neurodegenerative disorders. The present study investigated the effects of pioglitazone on depressive phenotypes and adult hippocampal neurogenesis in a rat model of PD that was induced by bilateral 6-hydroxydopamine (6-OHDA) infusions in the substantia nigra pars compact (SNpc)...
November 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29158022/activation-of-the-nrf2-signaling-pathway-and-neuroprotection-of-nigral-dopaminergic-neurons-by-a-novel-synthetic-compound-kms99220
#10
Ji Ae Lee, Hyo Jin Son, Ji Won Choi, Jinwoo Kim, Se Hee Han, Nari Shin, Ji Hyun Kim, Soo Jeong Kim, Jun Young Heo, Dong Jin Kim, Ki Duk Park, Onyou Hwang
The transcription factor Nrf2 is known to induce gene expression of antioxidant enzymes and proteasome subunits. Because both oxidative stress and protein aggregation have damaging effects on neurons, activation of the Nrf2 signaling should be beneficial against neurodegeneration. In this study, we report a novel synthetic morpholine-containing chalcone KMS99220 that confers neuroprotection. It showed high binding affinity to the Nrf2 inhibitory protein Keap-1 and increased nuclear translocation of Nrf2 and gene expression of the antioxidant enzymes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1, and the catalytic and modifier subunits of glutamate-cysteine ligase in dopaminergic CATH...
November 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29149768/mitochondrial-dna-changes-in-pedunculopontine-cholinergic-neurons-in-parkinson-s
#11
Alexander G Bury, Angela Pyle, Joanna L Elson, Laura Greaves, Christopher M Morris, Gavin Hudson, Ilse S Pienaar
In Parkinson's disease (PD), mitochondrial dysfunction associates with nigral dopaminergic neuronal loss. Cholinergic neuronal loss co-occurs, particularly within a brainstem structure, the pedunculopontine nucleus (PPN). We isolated single cholinergic neurons from post-mortem PPNs of aged controls and PD patients. Mitochondrial DNA (mtDNA) copy number and mtDNA deletions were increased significantly in PD patients compared to controls. Furthermore, compared to controls the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exceeding 60%, a level associated with deleterious effects on oxidative phosphorylation...
November 17, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29138117/melatonin-protects-against-behavioral-deficits-dopamine-loss-and-oxidative-stress-in-homocysteine-model-of-parkinson-s-disease
#12
Rajib Paul, Banashree Chetia Phukan, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Pallab Bhattacharya, Anupom Borah
AIM: Hyperhomocysteinemia and homocysteine (Hcy) mediated dopaminergic neurotoxicity is a matter of concern in the pathophysiology of Parkinson's disease (PD). Our previous study established the involvement of oxidative stress in the substantia nigra (SN) of Hcy rat model of PD; however, the role of antioxidants, such as melatonin, was not tested in this model. MAIN METHODS: Melatonin (10, 20 and 30mg/kg, i.p.) was administered to rats injected with Hcy in right SN (1...
November 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/29115484/lipoic-acid-alleviates-l%C3%A2-dopa%C3%A2-induced-dyskinesia-in-6%C3%A2-ohda-parkinsonian-rats-via-anti%C3%A2-oxidative-stress
#13
Su-Fang Zhang, Cheng-Long Xie, Jing-Ya Lin, Mei-Hua Wang, Xi-Jin Wang, Zhen-Guo Liu
Levodopa (L‑DOPA) is the gold standard for symptomatic treatment of Parkinson's disease (PD); however, long‑term therapy is associated with the emergence of L‑DOPA‑induced dyskinesia (LID). Nigral dopaminergic cell loss determines the degree of drug exposure and time required for the initial onset of LID. Accumulating evidence indicates that α‑lipoic acid (ALA) decreases this nigral dopaminergic cell loss. However, until now, the precise mechanisms of ALA have only been partially understood in LID...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111022/association-of-freezing-of-gait-with-nigral-iron-accumulation-in-patients-with-parkinson-s-disease
#14
Rajini M Naduthota, Arush Arun Honnedevasthana, Abhishek Lenka, Jitender Saini, Sairam Geethanath, Rose Dawn Bharath, Rita Christopher, Ravi Yadav, Arun Kumar Gupta, Pramod Kumar Pal
BACKGROUND AND PURPOSE: The objective of this work was to investigate whether patients with and without freezing of gait (FOG) in Parkinson's disease (PD) have differences in iron accumulation in substantia nigra using R2* relaxometry. MATERIALS AND METHODS: This study included seventeen PD patients with FOG [FOG (+)], equal number of age and gender matched patients without FOG [FOG (-)] and 34 healthy controls (HC). T2* images were obtained from a 3-Tesla MRI system using multi-echo sequence...
November 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29104779/the-spatial-organization-of-the-intranuclear-structures-of-human-brain-dopaminergic-neurons
#15
D E Korzhevskii, V V Gusel'nikova, O V Kirik, E G Sukhorukova, I P Grigorev
We studied the intranuclear localization of protein nucleophosmin (B23) and ubiquitin in the dopaminergic neurons of human substantia nigra (n = 6, age of 25-87 years) using immunohistochemistry and confocal laser microscopy. Intranuclear ubiquitin-immunopositive bodies that morphologically correspond to Marinesco bodies were found to be present in substantia nigra dopaminergic (tyrosine hydroxylase-immunopositive) neurons but absent in non-dopaminergic neurons. The number of bodies varied from 0 to 6 per cell nucleus...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/29100525/modulating-the-catalytic-activity-of-ampk-has-neuroprotective-effects-against-%C3%AE-synuclein-toxicity
#16
Wojciech Bobela, Sameer Nazeeruddin, Graham Knott, Patrick Aebischer, Bernard L Schneider
BACKGROUND: Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson's disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration. METHODS: Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo. RESULTS: Both AMPKα1 and α2 subunits have neuroprotective effects against human α-synuclein toxicity in nigral dopaminergic neurons...
November 3, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29089922/effects-of-subthalamic-and-nigral-stimulation-on-gait-kinematics-in-parkinson-s-disease
#17
Marlieke Scholten, Johannes Klemt, Melanie Heilbronn, Christian Plewnia, Bastiaan R Bloem, Friedemann Bunjes, Rejko Krüger, Alireza Gharabaghi, Daniel Weiss
Conventional subthalamic deep brain stimulation for Parkinson's disease (PD) presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG). Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr) area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN) stimulation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29089398/establishing-diagnostic-criteria-for-perry-syndrome
#18
Takayasu Mishima, Shinsuke Fujioka, Hiroyuki Tomiyama, Ichiro Yabe, Ryoichi Kurisaki, Naoki Fujii, Ryuji Neshige, Owen A Ross, Matthew J Farrer, Dennis W Dickson, Zbigniew K Wszolek, Nobutaka Hattori, Yoshio Tsuboi
OBJECTIVE: To establish international diagnostic criteria for Perry syndrome, a disorder characterised by clinical signs of parkinsonism, depression/apathy, weight loss, respiratory symptoms, mutations in the DCTN1 gene and TAR DNA-binding protein 43 (TDP-43) pathology. METHODS: Data from the published literature and newly identified patients were gathered and analysed during and after the International Symposium on Perry syndrome in Tokyo to identify diagnostic criteria for Perry syndrome...
October 31, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29064601/differential-involvement-of-nigral-subregions-in-idiopathic-parkinson-s-disease
#19
Young Hee Sung, Jongho Lee, Yoonho Nam, Hyeong-Geol Shin, Young Noh, Dong Hoon Shin, Eung Yeop Kim
In this study, the prevalence of abnormality in putative nigrosome 1 and nigrosome 4 (N1 and N4, respectively) was investigated in early versus late-stage idiopathic Parkinson's disease (IPD) patients. A total of 128 IPD patients (early stage[n = 89]; late stage[n = 39]) and 15 healthy subjects were scanned for high-resolution (0.5 × 0.5 × 1.0 mm(3) ) multiecho gradient-recalled echo MRI and dopamine transporter PET imaging. The MRI data were processed for susceptibility map-weighted imaging (SMWI) to improve a contrast-to-noise ratio, and the images were resliced at 0...
October 24, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29054882/parkinson-s-disease-associated-lrrk2-hyperactive-kinase-mutant-disrupts-synaptic-vesicle-trafficking-in-ventral-midbrain-neurons
#20
Ping-Yue Pan, Xianting Li, Jing Wang, James Powell, Qian Wang, Yuanxi Zhang, Zhaoyu Chen, Bridget Wicinski, Patrick Hof, Timothy A Ryan, Zhenyu Yue
Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has suggested a role of LRRK2, linked to the most frequent familial PD, in regulating synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear. Here we show that the most common PD mutation LRRK2 G2019S impairs SV endocytosis in ventral midbrain (MB) neurons including DA neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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