Fetal ventral mesencephalon of human and rat origin maintained in vitro and transplanted to 6-hydroxydopamine-lesioned rats gives rise to grafts rich in dopaminergic neurons

1996 ◽  
Vol 112 (1) ◽  
Author(s):  
Christian Spenger ◽  
NadiaS.K. Haque ◽  
Lorenz Studer ◽  
Ljudmila Evtouchenko ◽  
Bendicht Wagner ◽  
...  
2013 ◽  
Vol 543 ◽  
pp. 121-125 ◽  
Author(s):  
Cheong-Meng Chong ◽  
Zhong-Yan Zhou ◽  
Valentina Razmovski-Naumovski ◽  
Guo-Zhen Cui ◽  
Lun-Qing Zhang ◽  
...  

2021 ◽  
Author(s):  
Shouhai Wu ◽  
Tongxiang Lin ◽  
Yang Xu

Abstract BackgroundPaBing-II Formula (PB-II) is a traditional Chinese medicine developed to treat Parkinson's disease (PD). However, due to the complexity of PB-II and the difficulty of culturing human dopaminergic neurons (DAn) in vitro, the mechanism of PB-II to treat PD remains unclear. MethodsWe established the human induced pluripotent stem cells (iPSCs) and derived DAn from hiPSCs to study the protective effects of PB-II on DAn after oxidative stress, which plays an important role in PD pathogenesis. ResultsWe found that serum derived from rats that had ingested PB-II significantly protect hiPSC-derived DAn from reactive oxygen species (ROS). In addition, PB-II dependent serum can activate nuclear erythroid-derived factor 2 (Nrf2) responses, which are required for the neutralization of ROS. In addition, PB-II can activate the Nrf2/ARE signal pathway of midbrain dopaminergic neurons of PD rats induced with 6-hydroxydopamine (6-OHDA) injury, rescue DAn cells, and improve the symptoms of PD rats. ConclusionsPB-II significantly protects the DA neurons from oxidative stress by activating the Nrf2 pathway.


2019 ◽  
Vol 37 (2) ◽  
pp. 286-297 ◽  
Author(s):  
Magdalena Kurnik-Łucka ◽  
Gniewomir Latacz ◽  
Adrian Martyniak ◽  
Andrzej Bugajski ◽  
Katarzyna Kieć-Kononowicz ◽  
...  

AbstractSalsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline), widely available in many edibles, is considered to alter the function of dopaminergic neurons in the central nervous system and thus, multiple hypotheses on its either physiological and/or pathophysiological role have emerged. The aim of our work was to revisit its potentially neurotoxic and/or neuroprotective role through a series of both in vitro and in vivo experiments. Salsolinol in the concentration range 10–250 μM did not show any significant release of lactate dehydrogenase from necrotic SH-SY5Y cells and was able in the concentration of 50 and 100 μM to rescue SH-SY5Y cells from death induced by H2O2. Its neuroprotective effect against neurotoxin 6-hydroxydopamine was also determined. Salsolinol was found to decrease significantly the reactive oxygen species level in SH-SY5Y cells treated by 500 μM H2O2 and the caspase activity induced by 300 μM of H2O2 or 100 μM of 6-hydroxydopamine. Serum levels of TNFα and CRP of salsolinol-treated rats were not significantly different from control animals. Both TNFα and CRP served as indirect markers of neurotoxicity and/or neuroprotection. Although the neurotoxic properties of salsolinol have numerously been emphasized, its neuroprotective properties should not be neglected and need greater consideration.


Neuroscience ◽  
2008 ◽  
Vol 154 (2) ◽  
pp. 606-620 ◽  
Author(s):  
D. Moses ◽  
J. Drago ◽  
Y. Teper ◽  
I. Gantois ◽  
D.I. Finkelstein ◽  
...  

1999 ◽  
Vol 269 (3) ◽  
pp. 178-182 ◽  
Author(s):  
Karla Eggert ◽  
Jürgen Schlegel ◽  
Wolfgang Oertel ◽  
Cornelia Würz ◽  
Jürgen-Christian Krieg ◽  
...  

1997 ◽  
Vol 6 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Vandana Sable ◽  
K. Sailaja ◽  
Gomathy Gopinath ◽  
P. N. Tandon

Fetal ventral mesencephalon from the 15th gestational day was grafted into the striatum of neonatal and adult rats. In one group of adult rats, fetal nigra was transplanted into normal striatum. In a second group, the tissue was transplanted at sites where dopaminergic fibers were denervated with 6-hydroxydopamine. The behavior of the dopaminergic neurons and glial reactions were studied by staining with cresyl violet to localize the transplants and by immunolabeling tyrosine hydroxylase (TH) and glial fibrillary acidic protein. In normal adults, the transplants were small. At the edge of the transplants, TH-positive neurons were packed into clusters, and an interface without any significant crossover of TH-positive fibers was present. Glial reaction was minimal in and around the transplant. In the denervated striatum, transplants were generally larger than those in normal striatum and surrounded by a glial scar. TH-positive neurons were both closely packed and loosely arranged at the periphery of the transplants. Processes could be clearly defined and could be traced to the adjacent host striatum through the TH-free denervated area. In neonates, the transplants were large and at times extended beyond the striatum. Most TH-positive neurons were arranged linearly along the periphery of the transplant. Cell bodies were widely separated and a well-developed neuropil was present. Fibers from the transplant mingled freely with the host striatum without any interface. In all three transplant groups, tracing the TH-positive neurites was easy because they were thicker and coarser than other elements. No apparent glial reaction occurred in the neonates. Thus, the growth and maturation of dopaminergic neurons seemed to vary in different environments. The most conducive environment appears to be neonatal brain in which growth factors are readily available.


Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 315 ◽  
Author(s):  
Fábio G. Teixeira ◽  
Helena Vilaça-Faria ◽  
Ana V. Domingues ◽  
Jonas Campos ◽  
António J. Salgado

Parkinson’s Disease (PD) is characterized by the massive loss of dopaminergic neurons, leading to the appearance of several motor impairments. Current pharmacological treatments, such as the use of levodopa, are yet unable to cure the disease. Therefore, there is a need for novel strategies, particularly those that can combine in an integrated manner neuroprotection and neuroregeneration properties. In vitro and in vivo models have recently revealed that the secretome of mesenchymal stem cells (MSCs) holds a promising potential for treating PD, given its effects on neural survival, proliferation, differentiation. In the present study, we aimed to access the impact of human bone marrow MSCs (hBM-MSCs) secretome in 6-hydroxydopamine (6-OHDA) PD model when compared to levodopa administration, by addressing animals’ motor performance, and substantia nigra (SN), and striatum (STR) histological parameters by tyrosine hydroxylase (TH) expression. Results revealed that hBM-MSCs secretome per se appears to be a modulator of the dopaminergic system, enhancing TH-positive cells expression (e.g., dopaminergic neurons) and terminals both in the SN and STR when compared to the untreated group 6-OHDA. Such finding was positively correlated with a significant amelioration of the motor outcomes of 6-OHDA PD animals (assessed by the staircase test). Thus, the present findings support hBM-MSCs secretome administration as a potential therapeutic tool in treating PD, and although we suggest candidate molecules (Trx1, SEMA7A, UCHL1, PEDF, BDNF, Clusterin, SDF-1, CypA, CypB, Cys C, VEGF, DJ-1, Gal-1, GDNF, CDH2, IL-6, HSP27, PRDX1, UBE3A, MMP-2, and GDN) and possible mechanisms of hBM-MSCs secretome-mediated effects, further detailed studies are needed to carefully and clearly define which players may be responsible for its therapeutic actions. By doing so, it will be reasonable to presume that potential treatments that can, per se, or in combination modulate or slow PD may lead to a rational design of new therapeutic or adjuvant strategies for its functional modeling and repair.


2018 ◽  
Vol 7 (1) ◽  
Author(s):  
Ming-Shu Mo ◽  
Gui-Hua Li ◽  
Cong-Cong Sun ◽  
Shu-Xuan Huang ◽  
Lei Wei ◽  
...  

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