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astrocytes and MPTP

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https://www.readbyqxmd.com/read/30103794/connexin-30-deficiency-attenuates-a2-astrocyte-responses-and-induces-severe-neurodegeneration-in-a-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-hydrochloride-parkinson-s-disease-animal-model
#1
Atsushi Fujita, Hiroo Yamaguchi, Ryo Yamasaki, Yiwen Cui, Yuta Matsuoka, Ken-Ichi Yamada, Jun-Ichi Kira
BACKGROUND: The first pathology observed in Parkinson's disease (PD) is 'dying back' of striatal dopaminergic (DA) terminals. Connexin (Cx)30, an astrocytic gap junction protein, is upregulated in the striatum in PD, but its roles in neurodegeneration remain elusive. We investigated Cx30 function in an acute PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to wild-type (WT) and Cx30 knockout (KO) mice. METHODS: On days 1 and 7 after MPTP administration, we evaluated changes in astrocytic Cx30, Cx43, glial fibrillary acidic protein, and ionised calcium-binding adapter molecule 1 expression by immunostaining and biochemical analysis...
August 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/30006683/telmisartan-ameliorates-astroglial-and-dopaminergic-functions-in-a-mouse-model-of-chronic-parkinsonism
#2
Sathiya Sekar, Sugumar Mani, Barathidasan Rajamani, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Abid Bhat, Bipul Ray, Musthafa Mohamed Essa, Gilles J Guillemin, Saravana Babu Chidambaram
Many studies reported the neuroprotective effects of angiotensin II type 1 receptor (AT1R) antagonists in Parkinson's disease (PD). However, the role of AT1R blockade on astroglial, in turn, dopaminergic functions in chronic PD is still to be studied. In the present study, telmisartan (TEL; 3 and 10 mg/kg/day; p.o), was used to study the effects AT1R blockade on astrocytic and dopaminergic functions in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinsonism (250 mg/kg, i...
July 13, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/30006609/glucocorticoid-receptor-in-astrocytes-regulates-midbrain-dopamine-neurodegeneration-through-connexin-hemichannel-activity
#3
Layal Maatouk, Chenju Yi, Maria-Angeles Carrillo-de Sauvage, Anne-Claire Compagnion, Stéphane Hunot, Pascal Ezan, Etienne C Hirsch, Annette Koulakoff, Frank W Pfrieger, François Tronche, Luc Leybaert, Christian Giaume, Sheela Vyas
The precise contribution of astrocytes in neuroinflammatory process occurring in Parkinson's disease (PD) is not well characterized. In this study, using GRCx30CreERT2 mice that are conditionally inactivated for glucocorticoid receptor (GR) in astrocytes, we have examined the actions of astrocytic GR during dopamine neuron (DN) degeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results show significantly augmented DN loss in GRCx30CreERT2 mutant mice in substantia nigra (SN) compared to controls...
July 13, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29985188/aucubin-alleviates-glial-cell-activation-and-preserves-dopaminergic-neurons-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-parkinsonian-mice
#4
Ying-Li Zhu, Meng-Fei Sun, Xue-Bing Jia, Pei-Hao Zhang, Yi-Da Xu, Zhi-Lan Zhou, Zhou-Heng Xu, Chun Cui, Xue Chen, Xu-Sheng Yang, Yan-Qin Shen
Aucubin (AUC) is a major bioactive ingredient in Eucommia ulmoides, Plantain asiatica, and Aucuba japonica, and has been shown to exert anti-inflammatory, antioxidative, and neuroprotective effects. We explore the neuroprotective effects of AUC in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Mice were administered MPTP (30 mg/kg) daily for 5 days, followed by treatment with AUC for 7 days. Measurement of dopamine levels was performed by high-performance liquid chromatography and tyrosine hydroxylase expression was assessed by western blot...
September 5, 2018: Neuroreport
https://www.readbyqxmd.com/read/29959371/jia-jian-di-huang-yin-zi-decoction-exerts-neuroprotective-effects-on-dopaminergic-neurons-and-their-microenvironment
#5
Jingsi Zhang, Zhennian Zhang, Wen Zhang, Xiangting Li, Ting Wu, Tingting Li, Min Cai, Zhonghai Yu, Jun Xiang, Dingfang Cai
As a classical prescription of Traditional Chinese medicine, the Jia-Jian-Di-Huang-Yin-Zi (JJDHYZ) decoction has long been used to treat movement disorders. The present study evaluated the effects of JJDHYZ on dopaminergic (DA) neurons and their survival-enhancing microenvironment as well as the possible mechanisms involved using a mouse model of Parkinson's disease. In MPTP-lesioned mice, a high dosage of JJDHYZ (34 g/kg/day) attenuated the loss of DA neurons, reversed the dopamine depletion, and improved the expression of glial-derived neurotrophic factor (GDNF) compared to the untreated model group...
June 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29916143/mast-cell-proteases-activate-astrocytes-and-glia-neurons-and-release-interleukin-33-by-activating-p38-and-erk1-2-mapks-and-nf-%C3%AE%C2%BAb
#6
Duraisamy Kempuraj, Ramasamy Thangavel, Gvindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Smita Zaheer, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Iuliia Dubova, Gema Giler, Shelby Herr, Shankar S Iyer, Asgar Zaheer
Inflammatory mediators released from activated microglia, astrocytes, neurons, and mast cells mediate neuroinflammation. Parkinson's disease (PD) is characterized by inflammation-dependent dopaminergic neurodegeneration in substantia nigra. 1-Methyl-4-phenylpyridinium (MPP+ ), a metabolite of parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), induces inflammatory mediators' release from brain cells and mast cells. Brain cells' interaction with mast cells is implicated in neuroinflammation...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29907159/jnk-mediated-microglial-dicer-degradation-potentiates-inflammatory-responses-to-induce-dopaminergic-neuron-loss
#7
Qing Wang, Qian He, Yifei Chen, Wei Shao, Chao Yuan, Yizheng Wang
BACKGROUND: Amplified inflammation is important for the progression of Parkinson's disease (PD). However, how this enhanced inflammation is regulated remains largely unknown. Deletion of DICER leads to progressive dopamine neuronal loss and induces gliosis. We hypothesized that the homeostasis of microglial DICER would be responsible for the amplified inflammation in the mouse model of PD. METHODS: The microglia or C57BL/6 mice were treated or injected with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+ ), respectively, for the model establishment...
June 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29887945/manf-improves-the-mpp-mptp-induced-parkinson-s-disease-via-improvement-of-mitochondrial-function-and-inhibition-of-oxidative-stress
#8
Yigang Liu, Jingxing Zhang, Ming Jiang, Qiong Cai, Jianmin Fang, Lingjing Jin
OBJECTIVE: This study aimed to investigate the therapeutic effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) on the MPTP/MPP+ -induced model of Parkinson's disease (PD) and the potential mechanism. METHODS: Male C57BL/6 mice PD model with MPTP-induced were randomly injected bilaterally with MANF or PBS into the striatum. Two weeks later, Rotarod test, immunohistochemistry, and detection of dopamine (DA) and its metabolites, superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were performed...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29885849/ppar%C3%A3-%C3%AE-agonist-alleviates-nlrp3-inflammasome-mediated-neuroinflammation-in-the-mptp-mouse-model-of-parkinson-s-disease
#9
Linfang Chen, Liujun Xue, Jinlong Zheng, Xiangyang Tian, Yingdong Zhang, Qiang Tong
Recent studies have indicated that peroxisome proliferator-activated receptor β/δ (PPARß/δ) agonists exert neuroprotective effects in the model of Parkinson's disease (PD). Furthermore, PPARß/δ agonists have been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. Emerging evidence indicates that the nucleotide-binding domain and leucine-rich-repeat-protein 3 (NLRP3) inflammasome-mediated neuroinflammation plays a crucial role in the pathogenesis of PD. In the present study we investigate whether PPARß/δ agonists alleviate NLRP3-mediated neuroinflammation in the 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of PD...
June 8, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29743549/human-cortex-spheroid-with-a-functional-blood-brain-barrier-for-high-throughput-neurotoxicity-screening-and-disease-modeling
#10
Goodwell Nzou, R T Wicks, E E Wicks, S A Seale, C H Sane, A Chen, S V Murphy, J D Jackson, A J Atala
The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and application of human brain organoids developed from neuro-progenitor cells. While these models provide an excellent platform to study the effects of disease and genetic aberrances on brain development, they may not model the microvasculature and BBB of the adult human cortex...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29656363/2-pentadecyl-2-oxazoline-reduces-neuroinflammatory-environment-in-the-mptp-model-of-parkinson-disease
#11
Marika Cordaro, Rosalba Siracusa, Rosalia Crupi, Daniela Impellizzeri, Alessio Filippo Peritore, Ramona D'Amico, Enrico Gugliandolo, Rosanna Di Paola, Salvatore Cuzzocrea
Current pharmacological management of Parkinson disease (PD) does not provide for disease modification, but addresses only symptomatic features. Here, we explore a new approach to neuroprotection based on the use of 2-pentadecyl-2-oxazoline (PEA-OXA), the oxazoline derivative of the fatty acid amide signaling molecule palmitoylethanolamide (PEA), in an experimental model of PD. Daily oral treatment with PEA-OXA (10 mg/kg) significantly reduced behavioral impairments and neuronal cell degeneration of the dopaminergic tract induced by four intraperitoneal injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on 8-week-old male C57 mice...
April 14, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29626009/the-nurr1-ligand-1-1-bis-3-indolyl-1-p-chlorophenyl-methane-modulates-glial-reactivity-and-is-neuroprotective-in-mptp-induced-parkinsonism
#12
Sean L Hammond, Katriana A Popichak, Xi Li, Lindsay G Hunt, Evan H Richman, Pranav U Damale, Edwin K P Chong, Donald S Backos, Stephen Safe, Ronald B Tjalkens
The orphan nuclear receptor Nurr1 (also called nuclear receptor-4A2) regulates inflammatory gene expression in glial cells, as well as genes associated with homeostatic and trophic function in dopaminergic neurons. Despite these known functions of Nurr1, an endogenous ligand has not been discovered. We postulated that the activation of Nurr1 would suppress the activation of glia and thereby protect against loss of dopamine (DA) neurons after subacute lesioning with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
June 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29575325/neural-stem-cell-grafts-promote-astroglia-driven-neurorestoration-in-the-aged-parkinsonian-brain-via-wnt-%C3%AE-catenin-signaling
#13
Francesca L'episcopo, Cataldo Tirolo, Luca Peruzzotti-Jametti, Maria F Serapide, Nunzio Testa, Salvatore Caniglia, Beatrice Balzarotti, Stefano Pluchino, Bianca Marchetti
During aging-one the most potent risk factors for Parkinson's disease (PD)-both astrocytes and microglia undergo functional changes that ultimately hamper homoeostasis, defense, and repair of substantia nigra pars compacta (SNpc) midbrain dopaminergic (mDA) neurons. We tested the possibility of rejuvenating the host microenvironment and boosting SNpc DA neuronal plasticity via the unilateral transplantation of syngeneic neural stem/progenitor cells (NSCs) in the SNpc of aged mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced experimental PD...
March 25, 2018: Stem Cells
https://www.readbyqxmd.com/read/29519253/the-glycoprotein-gpnmb-attenuates-astrocyte-inflammatory-responses-through-the-cd44-receptor
#14
Matthew L Neal, Alexa M Boyle, Kevin M Budge, Fayez F Safadi, Jason R Richardson
BACKGROUND: Neuroinflammation is one of the hallmarks of neurodegenerative diseases, such as Parkinson's disease (PD). Activation of glial cells, including microglia and astrocytes, is a characteristic of the inflammatory response. Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that releases a soluble signaling peptide when cleaved by ADAM10 or other extracellular proteases. GPNMB has demonstrated a neuroprotective role in animal models of ALS and ischemia...
March 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29500411/astrocytic-jwa-deletion-exacerbates-dopaminergic-neurodegeneration-by-decreasing-glutamate-transporters-in-mice
#15
Rihua Wang, Xue Zhao, Jin Xu, Yifan Wen, Aiping Li, Ming Lu, Jianwei Zhou
Astrocytic JWA exerts neuroprotective roles by alleviating oxidative stress and inhibiting inflammation. However, the molecular mechanisms of how astrocytic JWA is involved in dopaminergic neurodegeneration in Parkinson's disease (PD) remain largely unknown. In this study, we found that astrocyte-specific JWA knockout mice (JWA CKO) exacerbated dopamine (DA) neuronal loss and motor dysfunction, and reduced the levels of DA and its metabolites in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model...
March 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29483868/microglia-polarization-gene-environment-interactions-and-wnt-%C3%AE-catenin-signaling-emerging-roles-of-glia-neuron-and-glia-stem-neuroprogenitor-crosstalk-for-dopaminergic-neurorestoration-in-aged-parkinsonian-brain
#16
REVIEW
Francesca L'Episcopo, Cataldo Tirolo, Maria F Serapide, Salvatore Caniglia, Nunzio Testa, Loredana Leggio, Silvia Vivarelli, Nunzio Iraci, Stefano Pluchino, Bianca Marchetti
Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29471030/neuroprotective-effects-of-fecal-microbiota-transplantation-on-mptp-induced-parkinson-s-disease-mice-gut-microbiota-glial-reaction-and-tlr4-tnf-%C3%AE-signaling-pathway
#17
Meng-Fei Sun, Ying-Li Zhu, Zhi-Lan Zhou, Xue-Bing Jia, Yi-Da Xu, Qin Yang, Chun Cui, Yan-Qin Shen
Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs)...
May 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29401614/depletion-of-microglia-augments-the-dopaminergic-neurotoxicity-of-mptp
#18
Xiaoxia Yang, Honglei Ren, Kristofer Wood, Minshu Li, Shenfeng Qiu, Fu-Dong Shi, Cungen Ma, Qiang Liu
The activation of microglia and the various substances they produce have been linked to the pathologic development of Parkinson's disease (PD), but the precise role of microglia in PD remains to be defined. The survival of microglia depends on colony-stimulating factor 1 receptor (CSF1R) signaling, and CSF1R inhibition results in rapid elimination of microglia in the central nervous system. Using a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, we showed that the depletion of microglia via the CSF1R inhibitor PLX3397 exacerbated the impairment of locomotor activities and the loss of dopaminergic neurons...
June 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29337144/early-activation-of-egr-1-promotes-neuroinflammation-and-dopaminergic-neurodegeneration-in-an-experimental-model-of-parkinson-s-disease
#19
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...
April 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29285094/neuroprotective-effects-of-astragaloside-iv-on-parkinson-disease-models-of-mice-and-primary-astrocytes
#20
Lei Xia, Dianxuan Guo, Bing Chen
Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Inflammation and neural degeneration are implicated in the pathogenesis of PD. Astragaloside IV (AS-IV) has been verified to attenuate inflammation. The current study aimed to investigate the role of AS-IV in PD and the possible molecular mechanisms. Pole, traction and swim tests were performed to examine the effects of AS-IV on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-generated behavioral deficiencies in vivo ...
December 2017: Experimental and Therapeutic Medicine
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