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https://www.readbyqxmd.com/read/29792848/subthalamic-nucleus-deep-brain-stimulation-protects-neurons-by-activating-autophagy-via-pp2a-inactivation-in-a-rat-model-of-parkinson-s-disease
#1
Ting-Ting Du, Ying-Chuan Chen, Yong-Quan Lu, Fan-Gang Meng, Hui Yang, Jian-Guo Zhang
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum...
May 21, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29782882/prolonged-increase-in-ser31-tyrosine-hydroxylase-phosphorylation-in-substantia-nigra-following-cessation-of-chronic-methamphetamine
#2
Michael F Salvatore, Vicki A Nejtek, Habibeh Khoshbouei
Methamphetamine (MA) exposure may increase the risk of motor or cognitive impairments similar to Parkinson's disease (PD) by middle age. Although damage to nigrostriatal or mesoaccumbens dopamine (DA) neurons may occur during or early after MA exposure, overt PD-like symptoms at a younger age may not manifest due to compensatory mechanisms to maintain DA neurotransmission. One possible compensatory mechanism is increased tyrosine hydroxylase (TH) phosphorylation. In the rodent PD 6-OHDA model, nigrostriatal lesion decreases TH protein in both striatum and substantia nigra (SN)...
May 18, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29778625/the-mediating-role-of-phosphodiesterase-type-4-in-the-dopaminergic-modulation-of-motor-impulsivity
#3
P R A Heckman, A Blokland, N P Van Goethem, B T J Van Hagen, J Prickaerts
The current study investigated the mediating role of phosphodiesterase type 4 (PDE4) regulated cAMP in the dopaminergic modulation of premature responding (action restraint) in rats. Response inhibition, which includes action restraint, finds its neurobiological origin in cortico-striatal-thalamic circuitry and can be modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cAMP/PKA signaling cascade. Areas in the prefrontal cortex are very sensitive to their neurochemical environment, including catecholamine levels...
May 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29774960/alteration-of-nociceptive-integration-in-the-spinal-cord-of-a-rat-model-of-parkinson-s-disease
#4
Keri-Ann Charles, Frédéric Naudet, Rabia Bouali-Benazzouz, Marc Landry, Philippe De Deurwaerdère, Pascal Fossat, Abdelhamid Benazzouz
BACKGROUND: Pain is a major non motor symptom that contributes to impaired quality of life in PD. However, its mechanism is unknown. OBJECTIVES AND METHODS: We sought to identify the pain phenotypes and parallel changes in spinal integration of peripheral stimuli in a rat model of PD induced by lesions of SN dopamine neurons, using behavioral plantar and von Frey tests as well as electrophysiology of the dorsal horn. RESULTS: We show that dopamine depletion by 6-OHDA induced hypersensitivity to mechanical and thermal stimuli...
May 18, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29772432/silymarin-prevents-apoptosis-through-inhibiting-the-bax-caspase-3-expression-and-suppresses-toll-like-receptor-4-pathway-in-the-snc-of-6-ohda-intoxicated-rats
#5
Rasool Haddadi, Alireza Mohajjel Nayebi, Shahla Eyvari Brooshghalan
BACKGROUND AND PURPOSE: Several lines of evidence show that apoptosis, oxidative stress and neuroinflammation are associated with the development of Parkinson's disease (PD). In the present study, we investigated the effect of pre-treatment with silymarin (SM) on oxidative stress, apoptosis and toll-like receptor 4 (TLR4) expression in substantia nigra pars copmacta (SNc) of 6-hydroxydopamine (6-OHDA)-lesioned rats. METHODS: Animals were pretreated with 100, 200 or 300 mg/kg of SM daily for 5 days and at 6th day 6-OHDA (8 μg/2 μl) was infused unilaterally into the central region of the SNc...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29766510/ineffectiveness-of-saxagliptin-as-a-neuroprotective-drug-in-6-ohda-lesioned-rats
#6
Joelle de Melo Turnes, Taysa Bervian Bassani, Leonardo C Souza, Maria A B F Vital
OBJECTIVES: To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. METHODS: Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days...
May 16, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29758248/beneficial-effect-of-etazolate-on-depression-like-behavior-and-learning-and-memory-impairment-in-a-model-of-parkinson-s-disease
#7
Karem H Alzoubi, Enas Mokhemer, Amjad N Abuirmeileh
The aim of this study was to evaluate etazolate against depression-like behavior and, learning and memory impairment induced by 6- hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD). This aim was achieved through comparing 6-OHDA lesioned rats in the presence and absence of etazolate. The 6-OHDA was used to induce lesion as a model of PD. Etazolate was administered at a dose of 1 mg/kg/day for 14 days, starting 7 days after lesion induction. Apomorphine-induced rotation test was used to evaluate 6-OHDA-induced motor deficits, tail suspension test was used to assess depression-like symptoms, and the radial arms water maze (RAWM) was used to evaluate special learning and memory functions...
May 11, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29755319/ambra1-mediated-mitophagy-counteracts-oxidative-stress-and-apoptosis-induced-by-neurotoxicity-in-human-neuroblastoma-sh-sy5y-cells
#8
Anthea Di Rita, Pasquale D'Acunzo, Luca Simula, Silvia Campello, Flavie Strappazzon, Francesco Cecconi
Therapeutic strategies are needed to protect dopaminergic neurons in Parkinson's disease (PD) patients. Oxidative stress caused by dopamine may play an important role in PD pathogenesis. Selective autophagy of mitochondria (mitophagy), mainly regulated by PINK1 and PARKIN, plays an important role in the maintenance of cell homeostasis. Mutations in those genes cause accumulation of damaged mitochondria, leading to nigral degeneration and early-onset PD. AMBRA1ActA is a fusion protein specifically expressed at the mitochondria, and whose expression has been shown to induce a powerful mitophagy in mammalian cells...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29746848/nitric-oxide-alterations-in-cardiovascular-system-of-rats-with-parkinsonism-induced-by-6-ohda-and-submitted-to-previous-exercise
#9
Lorena de Jager, Eric Diego Turossi Amorim, Bruno Fernando Cruz Lucchetti, Fernanda Novi Cortegoso Lopes, Carlos Cesar Crestani, Phileno Pinge-Filho, Marli Cardoso Martins-Pinge
Studies showed that physical exercise decreases the risk of developing Parkinson's disease (PD) as slowing its progression. During aerobic training, nitric oxide (NO) increases in the substantia nigra pars compacta (SNpc) of individuals with PD. However, no study has evaluated the effects of exercise on peripheral NO levels and its modulatory effects on cardiovascular dysfunctions of subjects with PD. Trained (T) or sedentary (S) animals underwent stereotactic surgery for bilateral 6-hydroxydopamine (6-OHDA) or vehicle microinfusion (Sham group)...
May 7, 2018: Life Sciences
https://www.readbyqxmd.com/read/29731707/the-neuroprotection-of-low-dose-morphine-in-cellular-and-animal-models-of-parkinson-s-disease-through-ameliorating-endoplasmic-reticulum-er-stress-and-activating-autophagy
#10
Bing Wang, Cun-Jin Su, Teng-Teng Liu, Yan Zhou, Yu Feng, Ya Huang, Xu Liu, Zhi-Hong Wang, Li-Hua Chen, Wei-Feng Luo, Tong Liu
Parkinson's disease (PD) is a common neurodegenerative disease characterized the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Brain endogenous morphine biosynthesis was reported to be impaired in PD patients and exogenous morphine attenuated 6-hydroxydopamine (6-OHDA)-induced cell death in vitro . However, the mechanisms underlying neuroprotection of morphine in PD are still unclear. In the present study, we investigated the neuroprotective effects of low-dose morphine in cellular and animal models of PD and the possible underlying mechanisms...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29726751/evaluation-of-the-antiparkinsonism-and-neuroprotective-effects-of-hydrogen-sulfide-in-acute-6-hydroxydopamine-induced-animal-model-of-parkinson-s-disease-behavioral-histological-and-biochemical-studies
#11
Mohammad Sarukhani, Hashem Haghdoost-Yazdi, Ali Sarbazi Golezari, Arvin Babayan-Tazehkand, Tahere Dargahi, Nafiseh Rastgoo
INTRODUCTION: Studies have shown that hydrogen sulfide (H2 S), a gaseous neurotransmitter, has neuroprotective effect. Here, we evaluated the neuroprotective activity of H2 S in acute 6-hydroxydopamine (6-OHDA) animal model of Parkinson's disease (PD). METHODS: 6-OHDA was injected through stereotaxic surgery into medial forebrain bundle (MFB) of the right hemisphere to induce severe and fast degeneration in dopaminergic neurons of substantia nigra (SN). NaHS, as donor of H2 S, was daily injected at doses of 3 and 5...
May 4, 2018: Neurological Research
https://www.readbyqxmd.com/read/29725300/salidroside-promotes-the-pathological-%C3%AE-synuclein-clearance-through-ubiquitin-proteasome-system-in-sh-sy5y-cells
#12
Tao Li, Yang Feng, Ruixin Yang, Leitao Wu, Ruru Li, Lu Huang, Qian Yang, Jianzong Chen
Parkinson's disease (PD) is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies (LBs) in the surviving SNc neurons. LBs formation is caused by the accumulation of α-synuclein (α-syn) or phosphorylated α-syn at serine-129 (pSer129-α-syn), which is implicated in the pathological progression of PD. Salidroside (Sal), the main active ingredient of the root of Rhodiola rosea L ., has been reported to have potent neuroprotective properties in our previous investigations...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29705946/extracellular-zn-2-influx-into-nigral-dopaminergic-neurons-plays-a-key-role-for-pathogenesis-of-6-hydroxydopamine-induced-parkinson-s-disease-in-rats
#13
Haruna Tamano, Ryusuke Nishio, Hiroki Morioka, Atsushi Takeda
Parkinson's disease (PD) is a progressive neurological disease characterized by a selective loss of nigrostriatal dopaminergic neurons. The exact cause of the neuronal loss remains unclear. Here, we report a unique mechanism of nigrostriatal dopaminergic neurodegeneration, in which extracellular Zn2+ influx plays a key role for PD pathogenesis induced with 6-hydroxydopamine (6-OHDA) in rats. 6-OHDA rapidly increased intracellular Zn2+ only in the substantia nigra pars compacta (SNpc) of brain slices and this increase was blocked in the presence of CaEDTA, an extracellular Zn2+ chelator, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, indicating that 6-OHDA rapidly increases extracellular Zn2+ influx via AMPA receptor activation in the SNpc...
April 29, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29705802/salidroside-protection-against-oxidative-stress-injury-through-the-wnt-%C3%AE-catenin-signaling-pathway-in-rats-with-parkinson-s-disease
#14
Dong-Mei Wu, Xin-Rui Han, Xin Wen, Shan Wang, Shao-Hua Fan, Juan Zhuang, Yong-Jian Wang, Zi-Feng Zhang, Meng-Qiu Li, Bin Hu, Qun Shan, Chun-Hui Sun, Jun Lu, Yuan-Lin Zheng
BACKGROUND/AIMS: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. METHODS: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo...
April 25, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29698669/fibroblast-growth-factor-20-is-protective-towards-dopaminergic-neurons-in-vivo-in-a-paracrine-manner
#15
Eugene L Boshoff, Edward J R Fletcher, Susan Duty
Neuroprotective strategies are an unmet medical need for Parkinson's disease. Fibroblast growth factor 20 (FGF20) enhances survival of cultured dopaminergic neurons but little is known about its in vivo potential. We set out to examine whether manipulation of the FGF20 system affected nigrostriatal tract integrity in rats, to identify which fibroblast growth factor receptors (FGFRs) might reside on dopaminergic neurons and to discover the source of endogenous FGF20 in the substantia nigra (SN). Male Sprague Dawley rats were subject to a partial 6-OHDA lesion alongside treatment with exogenous FGF20 or an FGFR antagonist...
April 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29694280/model-based-deconstruction-of-cortical-evoked-potentials-generated-by-subthalamic-nucleus-deep-brain-stimulation
#16
Karthik Kumaravelu, Chintan S Oza, Christina E Behrend, Warren M Grill
Parkinson's disease is associated with altered neural activity in the motor cortex. High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) suppresses parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal was to determine the neural origin of cEP using a two-step approach...
April 25, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29686643/inhibition-of-mtorc1-signaling-reverts-cognitive-and-affective-deficits-in-a-mouse-model-of-parkinson-s-disease
#17
Débora Masini, Alessandra Bonito-Oliva, Maëlle Bertho, Gilberto Fisone
Non-motor symptoms, including cognitive deficits and affective disorders, are frequently diagnosed in Parkinson's disease (PD) patients and are only partially alleviated by dopamine replacement therapy. Here, we used a 6-hydroxydopamine (6-OHDA) mouse model of PD to examine the effects exerted on non-motor symptoms by inhibition of the mammalian target of rapamycin complex 1 (mTORC1), which is involved in the control of protein synthesis, cell growth, and metabolism. We show that rapamycin, which acts as an allosteric inhibitor of mTORC1, counteracts the impairment of novel object recognition...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29686604/ultrasound-triggered-effects-of-the-microbubbles-coupled-to-gdnf-plasmid-loaded-pegylated-liposomes-in-a-rat-model-of-parkinson-s-disease
#18
Peijian Yue, Wang Miao, Lin Gao, Xinyu Zhao, Junfang Teng
Background: The purpose of this study was to investigate ultrasound-triggered effects of PEGylated liposomes-coupled microbubbles mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) plasmid (PLs-GDNF-MBs) on behavioral deficits and neuron loss in a rat model of Parkinson's disease (PD). Methods: The unloaded PLs-MBs were characterized for particle size, concentration and zeta potential. PD rat model was established by a unilateral 6-hydroxydopamine (6-OHDA) lesion. Rotational, climbing pole, and suspension tests were used to evaluate behavioral deficits...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29681884/glutathione-s-transferase-alpha-4-prevents-dopamine-neurodegeneration-in-a-rat-alpha-synuclein-model-of-parkinson-s-disease
#19
Michael Jewett, Elna Dickson, Kajsa Brolin, Matilde Negrini, Itzia Jimenez-Ferrer, Maria Swanberg
Parkinson's disease (PD) is a common, progressive neurodegenerative disease, which typically presents itself with a range of motor symptoms, like resting tremor, bradykinesia, and rigidity, but also non-motor symptoms such as fatigue, constipation, and sleep disturbance. Neuropathologically, PD is characterized by loss of dopaminergic cells in the substantia nigra pars compacta (SNpc) and Lewy bodies, neuronal inclusions containing α-synuclein (α-syn). Mutations and copy number variations of SNCA , the gene encoding α-syn, are linked to familial PD and common SNCA gene variants are associated to idiopathic PD...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29671234/gallic-acid-protects-6-ohda-induced-neurotoxicity-by-attenuating-oxidative-stress-in-human-dopaminergic-cell-line
#20
Y Chandrasekhar, G Phani Kumar, E M Ramya, K R Anilakumar
Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson's disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid...
April 18, 2018: Neurochemical Research
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