scholarly journals Intracerebral Transplantation of BDNF-overexpressing Human Neural Stem Cells (HB1.F3.BDNF) Promotes Migration, Differentiation and Functional Recovery in a Rodent Model of Huntington's Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 130-137
Author(s):  
Hyun Sook Kim ◽  
Iksoo Jeon ◽  
Jeong-Eun Noh ◽  
Hyunseung Lee ◽  
Kwan Soo Hong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Functional Recovery ◽  
Rodent Model ◽  
Human Neural Stem Cells ◽  
Intracerebral Transplantation

scholarly journals Human Neural Stem Cells Differentiate and Integrate, Innervating Implanted zQ175 Huntington’s Disease Mouse Striatum

2021 ◽  
Author(s):  
Sandra M. Holley ◽  
Jack C. Reidling ◽  
Carlos Cepeda ◽  
Alice Lau ◽  
Cindy Moore ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Pyramidal Neurons ◽  
Neurodegenerative Disorder ◽  
Functional Integration ◽  
Behavioral Deficits ◽  
Human Neural Stem Cells ◽  
Neuronal Populations

AbstractHuntington’s disease (HD), a genetic neurodegenerative disorder, primarily impacts the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that hNSCs transplanted into the striatum of HD mouse models differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here we show that 8-month implantation of hNSCs into the striatum of zQ175 HD mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) and reduces mutant Huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry and electron microscopy demonstrates that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells. Remarkably, hNSCs receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.

scholarly journals Transplants of Adult Mesenchymal and Neural Stem Cells Provide Neuroprotection and Behavioral Sparing in a Transgenic Rat Model of Huntington's Disease

Stem Cells ◽  
2014 ◽  
Vol 32 (2) ◽  
pp. 500-509 ◽  
Author(s):  
Julien Rossignol ◽  
Kyle Fink ◽  
Kendra Davis ◽  
Steven Clerc ◽  
Andrew Crane ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rat Model ◽  
Transgenic Rat ◽  
Transgenic Rat Model

scholarly journals Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in Human Huntington’s Disease Neural Stem Cells

2015 ◽  
Vol 5 (6) ◽  
pp. 1023-1038 ◽  
Author(s):  
Karen L. Ring ◽  
Mahru C. An ◽  
Ningzhe Zhang ◽  
Robert N. O’Brien ◽  
Eliana Marisa Ramos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Development ◽  
Therapeutic Targets ◽  
Genomic Analysis

Brain Transplantation of Immortalized Human Neural Stem Cells Promotes Functional Recovery in Mouse Intracerebral Hemorrhage Stroke Model

Stem Cells ◽  
2007 ◽  
Vol 25 (5) ◽  
pp. 1204-1212 ◽  
Author(s):  
Hong J. Lee ◽  
Kwang S. Kim ◽  
Eun J. Kim ◽  
Hyun B. Choi ◽  
Kwang H. Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intracerebral Hemorrhage ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Stroke Model ◽  
Human Neural Stem Cells

scholarly journals KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients

2017 ◽  
Vol 114 (23) ◽  
pp. E4676-E4685 ◽  
Author(s):  
Luisa Quinti ◽  
Sharadha Dayalan Naidu ◽  
Ulrike Träger ◽  
Xiqun Chen ◽  
Kimberly Kegel-Gleason ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Adaptor Protein ◽  
Negative Regulator ◽  
Model Systems ◽  
Human Model ◽  
Selective Activation ◽  
Primary Mouse

The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2. We further used this inducer to probe the functional consequences of selective activation of NRF2 signaling in Huntington's disease (HD) mouse and human model systems. Surprisingly, we discovered a muted NRF2 activation response in human HD neural stem cells, which was restored by genetic correction of the disease-causing mutation. In contrast, selective activation of NRF2 signaling potently repressed the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes. Moreover, in primary monocytes from HD patients and healthy subjects, NRF2 induction repressed expression of the proinflammatory cytokines IL-1, IL-6, IL-8, and TNFα. Together, our results demonstrate a multifaceted protective potential of NRF2 signaling in key cell types relevant to HD pathology.

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