Environmentally-Derived Carbolinium Analogs of MPP+ are Toxic to Dopaminergic Neurons in Vitro and in Vivo

1995 ◽  
pp. 537-543 ◽  
Author(s):  
Michael A. Collins ◽  
Edward J. Neafsey ◽  
Gail Zeevalk ◽  
Rudy Albores ◽  
G. Kindel ◽  
...  
Keyword(s):  
Dopaminergic Neurons

scholarly journals Neuroprotective Effect of Optimized Yinxieling Formula in 6-OHDA-Induced Chronic Model of Parkinson’s Disease through the Inflammation Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Renrong Wei ◽  
Cuiping Rong ◽  
Qingfeng Xie ◽  
Shouhai Wu ◽  
Yuchao Feng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Binding ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Cox 2

Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN)-striatum circuit, which is associated with glial activation and consequent chronic neuroinflammation. Optimized Yinxieling Formula (OYF) is a Chinese medicine that exerts therapeutical effect and antiinflammation property on psoriasis. Our previous study has proven that pretreatment with OYF could regulate glia-mediated inflammation in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Given that PD is a chronic degeneration disorder, this study applied another PD animal model induced by striatal injection of 6-hydroxydopamine (6-OHDA) to mimic the progressive damage of the SN-striatum dopamine system in rats. The OYF was administrated in the manner of pretreatment plus treatment. The effects of the OYF on motor behaviors were assessed with the apomorphine-induced rotation test and adjusting steps test. To confirm the effect of OYF on dopaminergic neurons and glia activation in this model, we analyzed the expression of tyrosine hydroxylase (TH) and glia markers, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP) in the SN region of the rat PD model. Inflammation-associated factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were further evaluated in this model and in interferon-γ- (INF-γ-) induced murine macrophages RAW264.7 cells. The results from the in vivo study showed that OYF reversed the motor behavioral dysfunction in 6-OHDA-induced PD rats, upregulated the TH expression, decreased the immunoreactivity of Iba-1 and GFAP, and downregulated the mRNA levels of TNF-α and COX-2. The OYF also trended to decrease the mRNA levels of IL-1β and iNOS in vivo. The results from the in vitro study showed that OYF significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. Therefore, this study suggests that OYF exerts antiinflammatory effects, which might be related to the protection of dopaminergic neurons in 6-OHDA-induced chronic neurotoxicity.

scholarly journals Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons

2018 ◽  
Author(s):  
Markus Riessland ◽  
Benjamin Kolisnyk ◽  
Tae Wan Kim ◽  
Jia Cheng ◽  
Jason Ni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cellular Senescence ◽  
Dopaminergic Neurons ◽  
Dna Binding Protein ◽  
Dopamine Neurons ◽  
Human Stem Cell ◽  
Transcriptional Program

AbstractCellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson‘s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson’s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons, both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes which are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor, p21, in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor to the pathology of Parkinson’s disease.

scholarly journals Anatomic and Biochemical Correlates of the Dopamine Transporter Ligand 11C-PE2I in Normal and Parkinsonian Primates: Comparison with 6-[18F]Fluoro-L-Dopa

2001 ◽  
Vol 21 (7) ◽  
pp. 782-792 ◽  
Author(s):  
Thomas Poyot ◽  
Françoise Condé ◽  
Marie-Claude Grégoire ◽  
Vincent Frouin ◽  
Christine Coulon ◽  
...  
Keyword(s):  
Gold Standard ◽  
Dopaminergic Neurons ◽  
Emission Tomography ◽  
Attractive Alternative ◽  
Input Rate ◽  
Nigrostriatal Pathway ◽  
Positron Emission ◽  
Neuroprotective Strategies

Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B′max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B′max = 26 and 36 pmol/mL) and reserpine-treated animals (B′max = 338 and 483 pmol/mL). In vivo11C-PE2I B′max values correlated with 18F-Dopa Ki values and in vitro125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.

scholarly journals Apelin-13 Protects Dopaminergic Neurons against Rotenone—Induced Neurotoxicity through the AMPK/mTOR/ULK-1 Mediated Autophagy Activation

2020 ◽  
Vol 21 (21) ◽  
pp. 8376
Author(s):  
Peng Chen ◽  
Youcui Wang ◽  
Leilei Chen ◽  
Ning Song ◽  
Junxia Xie
Keyword(s):  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Protective Effects ◽  
Gut Peptides ◽  
Neuroprotective Effects ◽  
Compound C ◽  
Apelin Receptor ◽  
Signaling Activation

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Several brain–gut peptides are able to exert neuroprotective effects on the nigrostriatal dopaminergic system. Apelin-13 is a neuropeptide, conveying potential neuroprotective activities. However, whether, and how, apelin-13 could antagonize rotenone-induced neurotoxicity has not yet been elucidated. In the present study, rotenone-treated SH-SY5Y cells and rats were used to clarify whether apelin-13 has protective effects on dopaminergic neurons, both in vivo and in vitro. The results showed that apelin-13 could protect SH-SY5Y cells from rotenone-induced injury and apoptosis. Apelin-13 was able to activate autophagy, and restore rotenone induced autophagy impairment in SH-SY5Y cells, which could be blocked by the autophagy inhibitor 3-Methyladenine. Apelin-13 activated AMPK/mTOR/ULK-1 signaling, AMPKα inhibitor compound C, as well as apelin receptor blockage via siRNA, which could block apelin-13-induced signaling activation, autophagy activation, and protective effects, in rotenone-treated SH-SY5Y cells. These results indicated that apelin-13 exerted neuroprotective properties against rotenone by stimulating AMPK/mTOR/ULK-1 signaling-mediated autophagy via the apelin receptor. We also observed that intracerebroventricular injection of apelin-13 could alleviate nigrostriatal dopaminergic neuron degeneration in rotenone-treated rats. Our findings provide new insights into the mechanism by which apelin-13 might attenuate neurotoxicity in PD.

scholarly journals A protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: Studies in vitro and in vivo

2007 ◽  
Vol 1127 ◽  
pp. 19-25 ◽  
Author(s):  
Lorraine Iacovitti ◽  
Angela E. Donaldson ◽  
Cheryl E. Marshall ◽  
Sokreine Suon ◽  
Ming Yang
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Dopaminergic Neurons ◽  
Embryonic Stem

scholarly journals Neuroprotective Effect and Mechanism of Thiazolidinedione on Dopaminergic Neurons In Vivo and In Vitro in Parkinson’s Disease

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yanqin Wang ◽  
Weilin Zhao ◽  
Ge Li ◽  
Jinhu Chen ◽  
Xin Guan ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Oral Treatment ◽  
Treated Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor

The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both in vitro and in vivo MPP+/MPTP induced PD models. In vivo experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor-γ coactivator of 1α (PGC-1α) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. From in vitro studies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1α, nuclear respiratory factor 1 (NRF1), NRF2, and mitochondria fusion 2 (Mfn2), and inhibited mitochondria fission 1 (Fis1). We show that protein levels of Bcl-2 and ERK were reduced in the MPP+-treated group compared with the control group. This effect was observed to be reversed upon treatment with 2,4-thiazolidinedione, as Bcl-2 and ERK expression levels were increased. We also observed that levels of the apoptotic protein Bax showed opposite changes compared to Bcl-2 and ERK levels. The results from this study confirm that pioglitazone/2,4-thiazolidinedione is able to activate PGC-1α and prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.

AAV.shRNA-mediated downregulation of ROCK2 attenuates degeneration of dopaminergic neurons in toxin-induced models of Parkinson's disease in vitro and in vivo

2015 ◽  
Vol 73 ◽  
pp. 150-162 ◽  
Author(s):  
Kim-Ann Saal ◽  
Jan C. Koch ◽  
Lars Tatenhorst ◽  
Éva M. Szegő ◽  
Vinicius Toledo Ribas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons

scholarly journals Evaluation of TH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons

2020 ◽  
Author(s):  
A Fiorenzano ◽  
J Nelander Wahlestedt ◽  
M Parmar
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Dopaminergic Neurons ◽  
Ethical Issues ◽  
Fetal Tissue ◽  
Cell Replacement Therapy ◽  
Progressive Degeneration ◽  
Gene Coding

AbstractThe focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson’s disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unprecedented opportunities to access a renewable source of cells suitable for PD therapeutic applications. To better understand the functional properties of stem-cell derived DA neurons, we generated targeted hPSC lines with the gene coding for Cre recombinase knocked into the TH locus. When combined with flexed GFP, they serve as reporter cell lines able to identify and isolate TH+ neurons in vitro and after transplantation in vivo. These TH-Cre lines provide a valuable genetic tool to manipulate DA neurons useful for the design of more precise DA differentiation protocols and the study of these cells after transplantation in pre-clinical animal models of PD.

scholarly journals Postmortem studies in Parkinson's disease

2004 ◽  
Vol 6 (3) ◽  
pp. 281-293 ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gold Standard ◽  
Dopaminergic Neurons ◽  
Nigrostriatal System ◽  
Regional Vulnerability ◽  
Environmental Agents ◽  
Postmortem Studies

No animal model to date perfectly replicates Parkinson's disease (PD) etiopathogenesis, and the anatomical organization of the nigrostriatal system differs considerably between species. Human postmortem material therefore remains the gold standard for both formulating hypotheses for subsequent testing in in vitro and in vivo PD models and verifying hypotheses derived from experimental PD models with regard to their validity in the human disease. This article focuses on recent and relevant fields in which human postmortem work has generated significant impact in our understanding of PD. These fields include Lewy body formation, regional vulnerability of dopaminergic neurons, oxidative/nitrative cellular stress, inflammation, apoptosis, infectious and environmental agents, and nondopaminergic lesions.

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