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https://www.readbyqxmd.com/read/29434538/glut9-mediated-urate-uptake-is-responsible-for-its-protective-effects-on-dopaminergic-neurons-in-parkinson-s-disease-models
#1
Mingxia Bi, Qian Jiao, Xixun Du, Hong Jiang
Considerable evidence has shown that elevated plasma or cerebrospinal fluid (CSF) urate levels correlated with a reduced risk of Parkinson's disease (PD). Based on its anti-oxidative properties, urate might serve as one of promising neuroprotective candidates for PD. However, how urate is transported through cell membranes to exert its effects inside the cells in PD is largely unknown. To elucidate this, we showed that increased intracellular urate exerted its neuroprotective effects against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in MES23...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29433982/bimolecular-fluorescence-complementation-of-alpha-synuclein-demonstrates-its-oligomerization-with-dopaminergic-phenotype-in-mice
#2
Waijiao Cai, Danielle Feng, Michael A Schwarzschild, Pamela J McLean, Xiqun Chen
Alpha-synuclein (αSyn) is encoded by the first causal gene identified in Parkinson's disease (PD) and is the main component of Lewy bodies, a pathological hallmark of PD. aSyn-based animal models have contributed to our understanding of PD pathophysiology and to the development of therapeutics. Overexpression of human wildtype αSyn by viral vectors in rodents recapitulates the loss of dopaminergic neurons from the substantia nigra, another defining pathological feature of the disease. The development of a rat model exhibiting bimolecular fluorescence complementation (BiFC) of αSyn by recombinant adeno-associated virus facilitates detection of the toxic αSyn oligomers species...
January 31, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29428223/angiotensin-1-7-ameliorates-6-hydroxydopamine-lesions-in-hemiparkinsonian-rats-through-activation-of-mas-receptor-pi3k-akt-bdnf-pathway-and-inhibition-of-angiotensin-ii-type-1-receptor-nf-%C3%AE%C2%BAb-axis
#3
Mostafa A Rabie, Mai A Abd El Fattah, Noha N Nassar, Hanan S El-Abhar, Dalaal M Abdallah
MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, improved motor performance and muscle coordination. On the molecular level, Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a positive feedback upregulates MASR...
February 8, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29428213/nigrostriatal-proteasome-inhibition-impairs-dopamine-neurotransmission-and-motor-function-in-minipigs
#4
Thea P Lillethorup, Andreas N Glud, Aage K O Alstrup, Trine W Mikkelsen, Erik H Nielsen, Hamed Zaer, Doris J Doudet, David J Brooks, Jens Christian H Sørensen, Dariusz Orlowski, Anne M Landau
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra leading to slowness and stiffness of limb movement with rest tremor. Using ubiquitin proteasome system inhibitors, rodent models have shown nigrostriatal degeneration and motor impairment. We translated this model to the Göttingen minipig by administering lactacystin into the medial forebrain bundle (MFB). Minipigs underwent positron emission tomography (PET) imaging with (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), a marker of vesicular monoamine transporter 2 availability, at baseline and three weeks after the unilateral administration of 100 μg lactacystin into the MFB...
February 8, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29422542/protection-of-nigral-dopaminergic-neurons-by-aav1-transduction-with-rheb-s16h-against-neurotoxic-inflammation-in-vivo
#5
Sehwan Kim, Gyeong Joon Moon, Yong-Seok Oh, Jungha Park, Won-Ho Shin, Jae Yeong Jeong, Kwang Shik Choi, Byung Kwan Jin, Nikolai Kholodilov, Robert E Burke, Hyung-Jun Kim, Chang Man Ha, Seok-Geun Lee, Sang Ryong Kim
We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson's disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2)...
February 9, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29422109/lack-of-pathogenic-potential-of-peripheral-%C3%AE-synuclein-aggregates-from-parkinson-s-disease-patients
#6
Ariadna Recasens, Iria Carballo-Carbajal, Annabelle Parent, Jordi Bové, Ellen Gelpi, Eduardo Tolosa, Miquel Vila
In Parkinson's disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism...
February 8, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29408408/combination-of-cdnf-and-deep-brain-stimulation-decreases-neurological-deficits-in-late-stage-model-parkinson-s-disease
#7
Antti Huotarinen, Anna-Maija Penttinen, Susanne Bäck, Merja H Voutilainen, Ulrika Julku, T Petteri Piepponen, Pekka T Männistö, Mart Saarma, Raimo Tuominen, Aki Laakso, Mikko Airavaara
Several neurotrophic factors (NTF) are shown to be neuroprotective and neurorestorative in pre-clinical animal models for Parkinson's disease (PD), particularly in models where striatal dopamine neuron innervation partially exists. The results of clinical trials on late-stage patients have been modest. Subthalamic deep brain stimulation (STN DBS) is a proven treatment for a selected group of advanced PD patients. The cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic protein, but its effects in animal models of late-stage PD have remained under-researched...
February 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29407467/neuroprotective-effects-of-voluntary-running-on-cognitive-dysfunction-in-an-%C3%AE-synuclein-rat-model-of-parkinson-s-disease
#8
Erin K Crowley, Yvonne M Nolan, Aideen M Sullivan
Parkinson's disease (PD) is no longer primarily classified as a motor disorder due to increasing recognition of the impact on patients of several nonmotor PD symptoms, including cognitive dysfunction. These nonmotor symptoms are highly prevalent and greatly affect the quality of life of patients with PD, and so, therapeutic interventions to alleviate these symptoms are urgently needed. The aim of this study was to investigate the potential neuroprotective effects of voluntary running on cognitive dysfunction in an adeno-associated virus-α-synuclein rat model of PD...
February 2, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29404956/bidirectional-neural-interaction-between-central-dopaminergic-and-gut-lesions-in-parkinson-s-disease-models
#9
Pablo Garrido-Gil, Ana I Rodriguez-Perez, Antonio Dominguez-Meijide, Maria J Guerra, Jose L Labandeira-Garcia
The exact mechanism of gut dysfunction in Parkinson's disease and, conversely, the role of gut pathology in brain dopaminergic degeneration are controversial. We investigated the effects of nigral lesions on the colonic neurotransmission, the effect of gut inflammation on the nigrostriatal dopaminergic function, and the possible involvement of the vagus nerve and the local renin-angiotensin system (RAS). Nigrostriatal dopamine depletion was performed by bilateral injection 6-hydroxydopamine, and gut inflammation was induced by dextran sulfate sodium salt treatment in rats and mice, respectively, with or without vagal disruption...
February 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29389881/tyrosine-hydroxylase-vesicular-monoamine-transporter-and-dopamine-transporter-mrna-expression-in-nigrostriatal-tissue-of-rats-with-pedunculopontine-neurotoxic-lesion
#10
Lisette Blanco-Lezcano, Esteban Alberti-Amador, Mei-Li Díaz-Hung, María Elena González-Fraguela, Bárbara Estupiñán-Díaz, Teresa Serrano-Sánchez, Liliana Francis-Turner, Javier Jiménez-Martín, Yamilé Vega-Hurtado, Isabel Fernández-Jiménez
BACKGROUND: The degeneration of the pedunculopontine nucleus (PPN) precedes the degeneration of the nigral cells in the pre-symptomatic stages of Parkinson's disease (PD). Although the literature recognizes that a lesion of the PPN increases the vulnerability of dopaminergic cells, it is unknown if this risk is associated with the loss of capability of handling the dopaminergic function. METHODS: In this paper, the effects of a unilateral neurotoxic lesion of the PPN in tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) mRNA expression in nigrostriatal tissue were evaluated...
February 1, 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29380907/dopamine-reuptake-transporter-single-photon-emission-computed-tomography-and-transcranial-sonography-as-imaging-markers-of-prediagnostic-parkinson-s-disease
#11
Alastair J Noyce, John Dickson, Richard N Rees, Jonathan P Bestwick, Ioannis U Isaias, Marios Politis, Gavin Giovannoni, Thomas T Warner, Andrew J Lees, Anette Schrag
OBJECTIVE: The objective of this study was to examine whether prediagnostic features of Parkinson's disease (PD) were associated with changes in dopamine reuptake transporter-single-photon emission computed tomography and transcranial sonography. METHODS: Prediagnostic features of PD (risk estimates, University of Pennsylvania Smell Identification Test, Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire, and finger-tapping scores) were assessed in a large cohort of older U...
January 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29355603/targeting-perk-signaling-with-the-small-molecule-gsk2606414-prevents-neurodegeneration-in-a-model-of-parkinson-s-disease
#12
Gabriela Mercado, Valentina Castillo, Paulina Soto, Nélida López, Jeffrey M Axten, Pablo Sardi, Jeroen J M Hoozemans, Claudio Hetz
Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to the progressive decline of motor control due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence suggest that altered proteostasis is a salient feature of PD, highlighting perturbations to the endoplasmic reticulum (ER), the main compartment involved in protein folding and secretion. PERK is a central ER stress sensor that enforces adaptive programs to recover homeostasis through a block of protein translation and the induction of the transcription factor ATF4...
January 17, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29349573/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-elevates-stimulus-evoked-release-of-dopamine-in-freely-moving-rats
#13
Juho-Matti Renko, Susanne Bäck, Merja H Voutilainen, T Petteri Piepponen, Ilkka Reenilä, Mart Saarma, Raimo K Tuominen
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson's disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29339765/mutations-in-bassoon-in-individuals-with-familial-and-sporadic-progressive-supranuclear-palsy-like-syndrome
#14
Ichiro Yabe, Hiroaki Yaguchi, Yasutaka Kato, Yasuo Miki, Hidehisa Takahashi, Satoshi Tanikawa, Shinichi Shirai, Ikuko Takahashi, Mari Kimura, Yuka Hama, Masaaki Matsushima, Shinsuke Fujioka, Takahiro Kano, Masashi Watanabe, Shin Nakagawa, Yasuyuki Kunieda, Yoshio Ikeda, Masato Hasegawa, Hiroshi Nishihara, Toshihisa Ohtsuka, Shinya Tanaka, Yoshio Tsuboi, Shigetsugu Hatakeyama, Koichi Wakabayashi, Hidenao Sasaki
Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer's disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339319/treatment-with-the-noradrenaline-re-uptake-inhibitor-atomoxetine-alone-and-in-combination-with-the-%C3%AE-2-adrenoceptor-antagonist-idazoxan-attenuates-loss-of-dopamine-and-associated-motor-deficits-in-the-lps-inflammatory-rat-model-of-parkinson-s-disease
#15
Justin D Yssel, Eoin O'Neill, Yvonne M Nolan, Thomas J Connor, Andrew Harkin
The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment with atomoxetine and idazoxan, a combination which serves to enhance the extra-synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects following delivery of an inflammatory stimulus, the bacterial endotoxin, lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss were rescued to varying degrees depending on the treatment...
January 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29337144/early-activation-of-egr-1-promotes-neuroinflammation-and-dopaminergic-neurodegeneration-in-an-experimental-model-of-parkinson-s-disease
#16
Qing Yu, Qiaoying Huang, Xiaoxiao Du, Shao Xu, Mingtao Li, Shanshan Ma
The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction of Egr-1 in the SNpc but not in the striatum...
January 11, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29317067/nigral-depigmentation-reflects-monoamine-exhaustion-as-initial-step-to-parkinson-s-disease
#17
Thomas Müller, Willi Kohlhepp
This hypothesis discusses exposure and response to various stressors as cause for chronic neurodegeneration. Predisposing genetic and environmental factors in conjunction with exposure to exogenous and endogenous toxins cause stress, which consumes dopamine and related biogenic amines. To compensate monoamine exhaustion, conversion of endogenous levodopa to dopamine by tyrosine hydroxylase is up regulated. Concomitantly, tyrosine mediated levodopa degradation to dopaquinone is reduced. Dopaquinone is the essential precursor of neuromelanin...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29288045/elevated-nuclear-phosphatase-and-tensin-homolog-pten-and-altered-insulin-signaling-in-substantia-nigral-region-of-patients-with-parkinson-s-disease
#18
Sathiya Sekar, Changiz Taghibiglou
Studies showed that 50-80% of Parkinson's disease (PD) patients have been reported with abnormal glucose tolerance. Alterations in glucose and energy metabolism serve as the early molecular event in PD. Although evidences support that the insulin resistance plays a major role in motor and non-motor complications of PD, the underlying mechanism in the pathogenesis of PD is unclear. To address this issue, we investigated the alterations in major components of insulin signaling in nuclear fraction (NF) and whole tissue homogenate (TH) of substantia nigral (SN) region obtained from postmortem PD brain and their age-matched controls...
December 26, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29279191/mr-findings-in-the-substantia-nigra-on-phase-difference-enhanced-imaging-in-neurodegenerative-parkinsonism
#19
Atsuhiko Sugiyama, Noriko Sato, Yukio Kimura, Miho Ota, Tomoko Maekawa, Daichi Sone, Mikako Enokizono, Miho Murata, Hiroshi Matsuda, Satoshi Kuwabara
INTRODUCTION: In Parkinson's disease (PD) patients, magnetic resonance (MR) imaging studies using phase difference enhanced imaging (PADRE) and susceptibility-weighted imaging (SWI) showed the obscuration of the boundary between the crural fibers and substantia nigra, and the absence of dorsolateral nigral hyperintensity, respectively. PADRE images have not been evaluated in other types of neurodegenerative parkinsonism, and PADRE and SWI images have not been compared. Here we evaluated PADRE and SWI images in patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), or PD and controls, and we compared the diagnostic values...
December 21, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29276478/application-of-the-physical-disector-principle-for-quantification-of-dopaminergic-neuronal-loss-in-a-rat-6-hydroxydopamine-nigral-lesion-model-of-parkinson-s-disease
#20
Katrine Fabricius, Pernille Barkholt, Jacob Jelsing, Henrik H Hansen
Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson's disease and in animal models of nigrostriatal degeneration...
2017: Frontiers in Neuroanatomy
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