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astrocytes and PD

Cara L Croft, Pedro E Cruz, Daniel H Ryu, Carolina Ceballos-Diaz, Kevin H Strang, Brittany M Woody, Wen-Lang Lin, Michael Deture, Edgardo Rodríguez-Lebrón, Dennis W Dickson, Paramita Chakrabarty, Yona Levites, Benoit I Giasson, Todd E Golde
It has been challenging to produce ex vivo models of the inclusion pathologies that are hallmark pathologies of many neurodegenerative diseases. Using three-dimensional mouse brain slice cultures (BSCs), we have developed a paradigm that rapidly and robustly recapitulates mature neurofibrillary inclusion and Lewy body formation found in Alzheimer's and Parkinson's disease, respectively. This was achieved by transducing the BSCs with recombinant adeno-associated viruses (rAAVs) that express α-synuclein or variants of tau...
February 15, 2019: Journal of Experimental Medicine
Shengchun Xu, Zemin Di, Yufeng He, Runjie Wang, Yuyang Ma, Rui Sun, Jing Li, Tao Wang, Yujun Shen, Shengyun Fang, Lijie Feng, Yuxian Shen
BACKGROUND: Extracellular accumulation of amyloid β-peptide (Aβ) is one of pathological hallmarks of Alzheimer's disease (AD) and contributes to the neuronal loss. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-inducible neurotrophic factor. Many groups, including ours, have proved that MANF rescues neuronal loss in several neurological disorders, such as Parkinson's disease and cerebral ischemia. However, whether MANF exerts its protective effect against Aβ neurotoxicity in AD remains unknown...
February 13, 2019: Journal of Neuroinflammation
MuhChyi Chai, Jun Kohyama
Non-cell-autonomous effects on neuronal cells are considered to be involved in the pathogenesis of neurodegenerative diseases but have yet to be mechanistically proven. In this issue of Stem Cell Reports, di Domenico et al. provide direct evidence that α-synuclein transferred from astrocytes exerts non-cell-autonomous neuronal dysfunction on dopaminergic neurons in Parkinson's disease (PD).
February 12, 2019: Stem Cell Reports
Jin-Sun Park, Yea-Hyun Leem, Jung-Eun Park, Do-Yeon Kim, Hee-Sun Kim
Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether β-Lapachone (β-LAP), a natural naphthoquinone compound isolated from the lapacho tree ( Tabebuia avellanedae ), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. β-LAP reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test...
February 8, 2019: Biomolecules & Therapeutics
Alice Kunzler, Camila Tiefensee Ribeiro, Juciano Gasparotto, Lyvia Lintzmaier Petiz, Helen Thais da Rosa Silva, Jeferson Delgado da Silva, Rafael Bortolin, Priscila Oliveira de Souza, Fabiano Barreto, Pedro Espitia-Perez, Carlos Eduardo Schnorr, Nauana Somensi, José Cláudio Fonseca Moreira, Daniel Pens Gelain
Vitamin A (retinol) is involved in signaling pathways regulating gene expression and was postulated to be a major antioxidant and anti-inflammatory compound of the diet. Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by loss of nigral dopaminergic neurons, involving oxidative stress and pro-inflammatory activation. The aim of the present study was to evaluate the neuroprotective effects of retinol oral supplementation against 6-hydroxydopamine (6-OHDA, 12 μg per rat) nigrostriatal dopaminergic denervation in Wistar rats...
February 7, 2019: Neurochemistry International
Amanda L Woerman, Abby Oehler, Sabeen A Kazmi, Jisoo Lee, Glenda M Halliday, Lefkos T Middleton, Steve M Gentleman, Daniel A Mordes, Salvatore Spina, Lea T Grinberg, Steven H Olson, Stanley B Prusiner
Previously, we reported that intracranial inoculation of brain homogenate from multiple system atrophy (MSA) patient samples produces neurological disease in the transgenic (Tg) mouse model TgM83+/- , which uses the prion protein promoter to express human α-synuclein harboring the A53T mutation found in familial Parkinson's disease (PD). In our studies, we inoculated MSA and control patient samples into Tg mice constructed using a P1 artificial chromosome to express wild-type (WT), A30P, and A53T human α-synuclein on a mouse α-synuclein knockout background [Tg(SNCA+/+ )Nbm, Tg(SNCA*A30P+/+ )Nbm, and Tg(SNCA*A53T+/+ )Nbm]...
January 28, 2019: Acta Neuropathologica
Md Jakaria, Md Ezazul Haque, Duk-Yeon Cho, Shofiul Azam, In-Su Kim, Dong-Kug Choi
NR4A2 is a nuclear receptor and a transcription factor, with distinctive physiological features. In the cell nuclei of the central nervous system, it is widely expressed and identified as a crucial regulator of dopaminergic (DA) neuronal differentiation, survival, and maintenance. Importantly, it has regulated different genes crucial for dopaminergic signals, and its expression has been diminished in both aged and PD post-mortem brains and reduced in PD patients. In microglia and astrocytes, the expression of NR4A2 has been found where it can be capable of inhibiting the expression of proinflammatory mediators; hence, it protected inflammation-mediated DA neuronal death...
January 25, 2019: Molecular Neurobiology
Xue Xue, Weiwei Zhang, Jifeng Zhu, Xiaojun Chen, Sha Zhou, Zhipeng Xu, Gang Hu, Chuan Su
Aquaporin-4 (AQP4), the main water-selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model, AQP4-deficient (AQP4-/- ) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH+ )-positive neurons than did wild-type AQP4 (AQP4+/+ ) controls. Microglia are the most important immune cells that mediate immune inflammation in PD...
January 25, 2019: Journal of Cellular and Molecular Medicine
Xiaojuan Wu, Xingjun Meng, Feng Tan, Zhigang Jiao, Xiuping Zhang, Huichun Tong, Xiaoliang He, Xiaodong Luo, Pingyi Xu, Shaogang Qu
Parkinson's disease (PD) features the degeneration and death of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies that contain alpha-synuclein (α-Syn). Among the numerous PD etiologies, glutamate excitotoxicity is a research hotspot, and glutamate transporters play key roles in this theory. It has been shown that the expression of glutamate transporter is regulated by microRNAs. In this study, we found that the expression and function of glutamate transporter type one (GLT-1) were significantly reduced and miR-543-3p was upregulated during the development of PD...
January 24, 2019: ACS Chemical Neuroscience
Shen-Zhao Lu, Yong-Shun Guo, Pei-Zhou Liang, Shu-Zhen Zhang, Shu Yin, Yan-Qing Yin, Xiao-Min Wang, Fei Ding, Xiao-Song Gu, Jia-Wei Zhou
Background: Parkinson's disease (PD) is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions (Lewy bodies) within some remaining neurons in the substantia nigra. Recently, astroglial inclusion body has also been found in some neurodegenerative diseases including PD. However, the underlying molecular mechanisms of how astroglial protein aggregation forms remain largely unknown. Here, we investigated the contribution of αB-crystallin (CRYAB), a small heat shock protein, in α-synuclein inclusion formation in astrocytes...
2019: Translational Neurodegeneration
Hyeonwi Son, Sujeong Kim, Doo-Hyuk Jung, Ji Hyeong Baek, Dong Hoon Lee, Gu Seob Roh, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi, Dong Kun Lee, Hyun Joon Kim
Glutamatergic synapses constitute a major excitatory neurotransmission system and are regulated by glutamate/glutamine (Gln) cycling between neurons and astrocytes. Gln synthetase (GS) produced by astrocytes plays an important role in maintaining the cycle. However, the significance of GS during synaptogenesis has not been clarified. GS activity and expression significantly increase from postnatal day (PD) 7 to 21, and GS is expressed prior to glial fibrillary acidic protein (GFAP) and is more abundant than GFAP throughout synaptogenesis...
January 22, 2019: Scientific Reports
Angelique di Domenico, Giulia Carola, Carles Calatayud, Meritxell Pons-Espinal, Juan Pablo Muñoz, Yvonne Richaud-Patin, Irene Fernandez-Carasa, Marta Gut, Armida Faella, Janani Parameswaran, Jordi Soriano, Isidro Ferrer, Eduardo Tolosa, Antonio Zorzano, Ana Maria Cuervo, Angel Raya, Antonella Consiglio
Parkinson's disease (PD) is associated with the degeneration of ventral midbrain dopaminergic neurons (vmDAns) and the accumulation of toxic α-synuclein. A non-cell-autonomous contribution, in particular of astrocytes, during PD pathogenesis has been suggested by observational studies, but remains to be experimentally tested. Here, we generated induced pluripotent stem cell-derived astrocytes and neurons from familial mutant LRRK2 G2019S PD patients and healthy individuals. Upon co-culture on top of PD astrocytes, control vmDAns displayed morphological signs of neurodegeneration and abnormal, astrocyte-derived α-synuclein accumulation...
January 6, 2019: Stem Cell Reports
Alice Filippini, Massimo Gennarelli, Isabella Russo
Accumulation of α-synuclein (α-syn) species in dopaminergic neurons is one of the main hallmarks of Parkinson's disease (PD). Several factors have been associated with α-syn aggregation process, including an impairment of the proper protein degradation, which might drive the neurons toward an alternative and/or additional clearance mechanism that involves the release of undigested material from the cell. It has been reported that extracellular α-syn, released by stressed and/or degenerating neurons, might widely contribute to the neuronal toxicity and degeneration...
January 14, 2019: Cellular and Molecular Neurobiology
Orhan Tansel Korkmaz, Neşe Tunçel
Parkinson's disease is the second most common neurodegenerative disorder in adults over the age of 65. The characteristic symptoms of Parkinson's disease, such as resting tremor, muscular rigidity, bradykinesia, postural instability and gait imbalance, are thought to be a result of the progressive degeneration of the dopaminergic neurons of the substantia nigra compacta, resulting in insufficient dopamine integrated signalling on GABAergic medium spiny neurons in the striatum. Despite tremendous research, the molecular mechanisms underlying the pathogenesis of neurodegeneration in Parkinson's disease have remained largely unknown...
January 11, 2019: Current Pharmaceutical Design
Tim Prorok, Malabendu Jana, Dhruv Patel, Kalipada Pahan
Parkinson's disease (PD) is the second most common devastating human neurodegenerative disorder and despite intense investigation, no effective therapy is available for PD. Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, is a precursor for the synthesis of a huge number of plant substances. This study highlights the neuroprotective effect of cinnamic acid in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Oral administration of cinnamic acid protected tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) and TH fibers in the striatum of MPTP-insulted mice...
January 5, 2019: Neurochemical Research
Chao Wu, Lan-De Xue, Lin-Wang Su, Jian-Li Xie, Huan Jiang, Xi-Jiao Yu, Hong-Mei Liu
OBJECTIVE: Neural stem cells (NSCs) are multipotent stem cells that generating various neural cells, including neurons, astrocytes and oligodendrocytes. This showed that NSCs is an ideal candidate in the application of neural disease treatment. In the current study, we established a simple and efficient method to promote the viability and induce the differentiation of NSCs by stimulating with magnesium. METHODS: The proliferation and differentiation of NSCs was determined by MTT assay and immunostaining...
December 30, 2018: Neurological Research
Jiayin Zhou, Yuanyuan Deng, Fei Li, Caixia Yin, Jingshan Shi, Qihai Gong
Inflammation in central nervous system (CNS) plays a vital role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (DLB), HIV-related dementia and traumatic brain injury. Icariside II (ICS II), an active flavonoid compound derived from a Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess a neuroprotective effect on AD model. However, whether ICS II has a directly protective effect on acute neuroinflammation remains still unclear...
December 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Katarzyna Kuter, Łukasz Olech, Norbert A Dencher
Partial degeneration of dopaminergic neurons in the substantia nigra (SN), induces locomotor disability in animals but with time it is spontaneously compensated for by neurons surviving in the tissue by increasing their functional efficiency. Such compensation probably increases energy requirements and astrocyte support could be essential for this ability. We studied the effect of degeneration of dopaminergic neurons induced by the selective toxin 6-hydroxydopamine and/or death of 30% of astrocytes induced by chronic infusion of the glial toxin fluorocitrate on functioning of the mitochondrial electron transfer chain (ETC) complexes (Cxs) I, II, IV and their higher assembled forms, supercomplexes in the rat SN...
December 19, 2018: Mitochondrion
Takuma Ohmichi, Masato Mitsuhashi, Harutsugu Tatebe, Takashi Kasai, Omar M Ali El-Agnaf, Takahiko Tokuda
INTRODUCTION: There is still a substantial unmet need for blood-based biomarkers to make an objective diagnosis of Parkinson's disease (PD) and the parkinsonism-plus syndromes. This study is aimed to determine whether enumeration of brain-derived exosomes (BDEs) in plasma is informative in the diagnosis of those diseases. METHODS: We have developed a specific method to enumerate the plasma levels of neuron-derived, astrocyte-derived, and oligodendrocyte-derived exosomes (NDEs, ADEs and ODEs, respectively), and quantified them individually in patients with PD (n = 15), multiple system atrophy (MSA, n = 15), progressive supranuclear palsy (PSP, n = 7) and disease controls (n = 15)...
November 20, 2018: Parkinsonism & related Disorders
Mona Dehhaghi, Vanessa Tan, Benjamin Heng, Fatemeh Mohammadipanah, Gilles J Guillemin
Astrocytes, the main non-neuronal cells in the brain, have significant roles in the maintenance and survival of neurons. Oxidative stress has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Myxobacteria produce a wide range of bioactive metabolites with notable structures and modes of action, which introduce them as potent natural product producers. In the present study, we evaluated the effects of myxobacterial extracts on hydrogen peroxide (H2 O2 ) mediated toxicity on primary human astrocytes...
November 26, 2018: Neuroscience
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