Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1

Fedele, Valentina; Roybon, Laurent; Nordström, Ulrika; Li, Jiayi; Brundin, Patrik

doi:10.1016/j.neuroscience.2010.08.022

Cited by 47 publications

(30 citation statements)

References 34 publications

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“…Indeed, NeuroD1 -deficient mice fail to develop a hippocampal granule cell layer (93). Survival and differentiation of adult born neurons from neural stem cells also require NeuroD1 (94), and low NeuroD1 expression reduces neurogenesis (95). Knockout of related Neurog2 also profoundly affects development of the dentate gyrus (96) whereas double-knockout of Olig1/2 results in total loss of oligodendrocytes throughout the brain (97).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Identification of Basic Helix–Loop–Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus

et al. 2017

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Glucocorticoids regulate hippocampal function in part by modulating gene expression through the glucocorticoid receptor (GR). GR binding is highly cell type specific, directed to accessible chromatin regions established during tissue differentiation. Distinct classes of GR binding sites are dependent on the activity of additional signal-activated transcription factors that prime chromatin toward context-specific organization. We hypothesized a stress context dependency for GR binding in hippocampus as a consequence of rapidly induced stress mediators priming chromatin accessibility. Using chromatin immunoprecipitation sequencing to interrogate GR binding, we found no effect of restraint stress context on GR binding, although analysis of sequences underlying GR binding sites revealed mechanistic detail for hippocampal GR function. We note enrichment of GR binding sites proximal to genes linked to structural and organizational roles, an absence of major tethering partners for GRs, and little or no evidence for binding at negative glucocorticoid response elements. A basic helix–loop–helix motif closely resembling a NeuroD1 or Olig2 binding site was found underlying a subset of GR binding sites and is proposed as a candidate lineage-determining transcription factor directing hippocampal chromatin access for GRs. Of our GR binding sites, 54% additionally contained half-sites for nuclear factor (NF)-1 that we propose as a collaborative or general transcription factor involved in hippocampal GR function. Our findings imply a dose-dependent and context-independent action of GRs in the hippocampus. Alterations in the expression or activity of NF-1/basic helix–loop–helix factors may play an as yet undetermined role in glucocorticoid-related disease susceptibility and outcome by altering GR access to hippocampal binding sites.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Identification of Basic Helix–Loop–Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus

et al. 2017

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“…This resulted in a reduction of newly generated neurons, although, in most reports, neuronal differentiation was not compromised. Several studies also observed a reduced number of neuroblasts and immature neurons (Kohl et al 2007;Peng et al 2008;Fedele et al 2011).…”

Section: Adult Neurogenesis In Transgenic Animal Models Of Hdmentioning

confidence: 98%

Adult Neurogenesis in Neurodegenerative Diseases: Figure 1.

Winner¹,

Winkler

2015

Cold Spring Harb Perspect Biol

266

213

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“…The R6/2 line exhibits early impaired hippocampal neurogenesis at the age of 5.5 weeks, including a defi cit in stem cell proliferation as early as 2 weeks of age, determined by PCNA and Ki-67 stainings (Gil et al 2005 ). While some confl icting data were presented by Phillips et al, where the number of DCX-expressing neuroblasts remained unchanged in R6/2 and non-tg mice without kainic acid treatment (Phillips et al 2005 ), severely impaired DG neurogenesis, including reduction in stem cell proliferation and number of neuroblasts and immature neurons, was confi rmed (Kohl et al 2007 ;Peng et al 2008 ;Fedele et al 2011 ). Moreover, the proliferative capacity of DG-derived neural stem cells from R6/2 mice in vitro was impaired (Phillips et al 2005 ).…”

Section: Hippocampal Neurogenesis In Transgenic Animal Models Of Hdmentioning

confidence: 94%

“…To date, it remains under debate whether small oligomers or larger inclusion bodies are the deleterious species of mutant htt (Arrasate et al 2004 ;Legleiter et al 2010 ). Moreover, in the context of hippocampal neurogenesis, it seems interesting to note that in R6/2 transgenic mice, mutant htt aggregates were only present in mature, NeuN-expressing neurons but not in immature neuroblasts expressing DCX (Kohl et al 2007 ) or immature neurons expressing NeuroD (Fedele et al 2011 ) (see Fig. 1 ).…”

Section: Mechanisms Underlying Impaired Hippocampal Neurogenesis In Hdmentioning

confidence: 98%

Hippocampal Neurogenesis in Neurodegenerative Movement Disorders

Kohl

Winner

Winkler

2014

Neural Stem Cells in Development, Adulthood and Disease

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Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1

Cited by 47 publications

References 34 publications

Genome-Wide Identification of Basic Helix–Loop–Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus

Genome-Wide Identification of Basic Helix–Loop–Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus

Adult Neurogenesis in Neurodegenerative Diseases: Figure 1.

Hippocampal Neurogenesis in Neurodegenerative Movement Disorders

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