scholarly journals Neural stem cells restore cognitive function in Parkinsonian macaques

Author(s):  
Julien Vezoli ◽  
Florence Wianny ◽  
Kwamivi Dzahini ◽  
Karim Fifel ◽  
Charles Wilson ◽  
...  

Abstract Cognitive deficits as well as disorders of sleep and biological rhythms constitute non-motor symptoms that significantly impact quality of life in Parkinson’s disease patients. Few studies have evaluated the impact of cell replacement therapy on such non-motor symptoms. Here we used a multidisciplinary approach to assess the therapeutic potential of bilateral grafts of neural stem cells in a macaque model of Parkinson’s disease on both motor and non-motor markers of functional recovery. Grafts led to varying degrees of functional recovery while sham experiments did not. We show unprecedented recovery from cognitive symptoms in addition to a clear clinical motor recuperation. Motor and cognitive recovery but not circadian rhythm recovery correlated with the degree of graft integration into the host environment and with in-vivo levels of striatal dopaminergic transporters and function. This study provides empirical evidence that neural stem cells transplantation efficiently restore function at multiple levels in Parkinsonian non-human primates. We demonstrate the promising potential of multiple-sites neural stem cells grafts for Parkinson’s disease but furthermore underline the crucial importance of such multidisciplinary approaches for an effective clinical translation.

2020 ◽  
Author(s):  
Florence Wianny ◽  
Kwamivi Dzahini ◽  
Karim Fifel ◽  
Charles R.E. Wilson ◽  
Agnieszka Bernat ◽  
...  

Cognitive deficits as well as disorders of sleep and biological rhythms constitute non-motor symptoms that significantly impact quality of life in Parkinson′s disease patients. Few studies have evaluated the impact of cell replacement therapy on such non-motor symptoms. We used a multidisciplinary approach to assess the therapeutic potential of bilateral grafts of neural stem cells in a macaque model of Parkinson′s disease on both motor and non-motor markers of functional recovery. Grafts led to varying degrees of functional recovery while sham experiments did not. Motor and cognitive but not circadian rhythm recovery correlated with the degree of graft integration into the host environment and dopaminergic function. Transplantation of neural stem cells thus restore function at multiple levels in the parkinsonian monkeys.


2021 ◽  
Vol 19 ◽  
Author(s):  
Yu Jin Jung ◽  
Han-Joon Kim ◽  
Sun Ha Paek ◽  
Beomseok Jeon

: Sleep-wake disturbances (SWD) are one of the most common non-motor symptoms in Parkinson's disease (PD) and can appear in the early stage even before the onset of motor symptoms. Deep brain stimulation (DBS) is an established treatment for the motor symptoms in patients with advanced PD. However, the effect of DBS on SWD and its specific mechanisms are not widely understood and remain controversial. In addition to the circuit-mediated direct effect, DBS may improve SWD by an indirect effect such as the resolution of nocturnal motor complications and a reduction of dopaminergic medication. Here, the authors review the recent literatures regarding the impact of DBS on SWD in patients with PD. Furthermore, the selection of the DBS targets and the specific effects of applying DBS to each target on SWD in PD are also discussed.


2014 ◽  
Vol 4 (2) ◽  
pp. 289-300 ◽  
Author(s):  
Lisa Klingelhoefer ◽  
Michael Samuel ◽  
K. Ray Chaudhuri ◽  
Keyoumars Ashkan

2019 ◽  
Vol 64 ◽  
pp. 138-144 ◽  
Author(s):  
Jarosław Dulski ◽  
Michał Schinwelski ◽  
Agnieszka Konkel ◽  
Karol Grabowski ◽  
Witold Libionka ◽  
...  

2011 ◽  
Vol 26 (3) ◽  
pp. 399-406 ◽  
Author(s):  
Pablo Martinez-Martin ◽  
Carmen Rodriguez-Blazquez ◽  
Monica M. Kurtis ◽  
K. Ray Chaudhuri ◽  

2016 ◽  
Vol 23 (5) ◽  
pp. 854-860 ◽  
Author(s):  
K. M. Prakash ◽  
N. V. Nadkarni ◽  
W.-K. Lye ◽  
M.-H. Yong ◽  
E.-K. Tan

2005 ◽  
Vol 14 (4) ◽  
pp. 193-202 ◽  
Author(s):  
M. Y. Ryu ◽  
M. A. Lee ◽  
Y. H. Ahn ◽  
K. S. Kim ◽  
S. H. Yoon ◽  
...  

Neural stem cells (NSCs) of the central nervous system (CNS) recently have attracted a great deal of interest not only because of their importance in basic research on neural development, but also in terms of their therapeutic potential in neurological diseases, such as Parkinson's disease (PD). To examine if genetically modified NSCs are a suitable source for the cell and gene therapy of PD, an immortalized mouse NSC line, C17.2, was transduced with tyrosine hydroxylase (TH) gene and with GTP cyclohydrolase 1 (GTPCH1) gene, which are important enzymes in dopamine biosynthesis. The expression of TH in transduced C17.2-THGC cells was confirmed by RT-PCR, Western blot analysis, and immunocytochemistry, and expression of GTPCH1 by RT-PCR. The level of L-DOPA released by C17.2-THGC cells, as determined by HPLC assay, was 3793 pmol/106 cells, which is 760-fold higher than that produced by C17.2-TH cells, indicating that GTPCH1 expression is important for L-DOPA production by transduced C17.2 cells. Following the implantation of C17.2-THGcC NSCs into the striata of parkinsonian rats, a marked improvement in amphetamine-induced turning behavior was observed in parkinsonian rats grafted with C17.2-THGC cells but not in the control rats grafted with C17.2 cells. These results indicate that genetically modified NSCs grafted into the brain of the parkinsonian rats are capable of survival, migration, and neuronal differentiation. Collectively, these results suggest that NSCs have great potential as a source of cells for cell therapy and an effective vehicle for therapeutic gene transfer in Parkinson's disease.


2017 ◽  
Vol 18 (1) ◽  
pp. 224 ◽  
Author(s):  
Dong-Hee Choi ◽  
Ji-Hye Kim ◽  
Sung Kim ◽  
Kyuree Kang ◽  
Dong Han ◽  
...  

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