scholarly journals Human iPSC‐derived neural precursor cells differentiate into multiple cell types to delay disease progression following transplantation into YAC128 Huntington's disease mouse model

2021 ◽  
Author(s):  
Hyun Jung Park ◽  
Juhyun Jeon ◽  
Jiwoo Choi ◽  
Ji Yeon Kim ◽  
Hyun Sook Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Disease Progression ◽  
Cell Types ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Delay Disease Progression ◽  
Multiple Cell ◽  
Human Ipsc

scholarly journals Circadian-based Treatment Strategy Effective in the BACHD Mouse Model of Huntington’s Disease

2018 ◽  
Vol 33 (5) ◽  
pp. 535-554 ◽  
Author(s):  
Daniel S. Whittaker ◽  
Dawn H. Loh ◽  
Huei-Bin Wang ◽  
Yu Tahara ◽  
Dika Kuljis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Progression ◽  
Sleep Onset ◽  
Lifestyle Changes ◽  
Disease Stage ◽  
Preclinical Model ◽  
Delay Disease Progression ◽  
Circadian Dysfunction

Huntington’s disease (HD) patients suffer from progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep-wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and excessive fatigue. The BACHD mouse model exhibits many HD core symptoms including circadian dysfunction. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early interventions that improve circadian rhythmicity could benefit HD symptoms and delay disease progression. We evaluated the effects of time-restricted feeding (TRF) on the BACHD mouse model. At 3 months of age, the animals were divided into 2 groups: ad lib and TRF. The TRF-treated BACHD mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle (ZT 15-21) of the period when mice are normally active (ZT 12-24). Following 3 months of treatment (when mice reached the early disease stage), the TRF-treated BACHD mice showed improvements in their locomotor activity and sleep behavioral rhythms. Furthermore, we found improved heart rate variability, suggesting that their autonomic nervous system dysfunction was improved. On a molecular level, TRF altered the phase but not the amplitude of the PER2::LUC rhythms measured in vivo and in vitro. Importantly, treated BACHD mice exhibited improved motor performance compared with untreated BACHD controls, and the motor improvements were correlated with improved circadian output. It is worth emphasizing that HD is a genetically caused disease with no known cure. Lifestyle changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of circadian-based treatment strategies in a preclinical model of HD.

scholarly journals Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells

2013 ◽  
Vol 394 (12) ◽  
pp. 1623-1636 ◽  
Author(s):  
The Duy Nguyen ◽  
Darius Widera ◽  
Johannes Greiner ◽  
Janine Müller ◽  
Ina Martin ◽  
...  
Keyword(s):  
Cell Types ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Early Passage ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Prolonged Cultivation ◽  
Tumorigenic Transformation

Abstract Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.

scholarly journals Bioluminescence‐driven optogenetic activation of transplanted neural precursor cells improves motor deficits in a Parkinson's disease mouse model

2018 ◽  
Vol 98 (3) ◽  
pp. 458-468 ◽  
Author(s):  
Jessica R. Zenchak ◽  
Brandon Palmateer ◽  
Nicolai Dorka ◽  
Tariq M. Brown ◽  
Lina‐Marie Wagner ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Motor Deficits ◽  
Neural Precursor

The mystery of intracellular developmental programmes and timers

2006 ◽  
Vol 34 (5) ◽  
pp. 663-670 ◽  
Author(s):  
M. Raff
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Animal Development ◽  
Over Time

There has been a revolution in understanding animal development in the last 25 years or so, but there is at least one area of development that has been relatively neglected and therefore remains largely mysterious. This is the intracellular programmes and timers that run in developing precursor cells and change the cells over time. The molecular mechanisms underlying these programmes are largely unknown. My colleagues and I have studied such programmes in two types of rodent neural precursor cells: those that give rise to oligodendrocytes, which make myelin in the CNS (central nervous system), and those that give rise to the various cell types in the retina.

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