Valproic acid promotes neuronal differentiation by induction of proneural factors in association with H4 acetylation

Yu, In Tag; Park, Jin Yong; Kim, Sung Hyun; Lee, Jeong Sik; Kim, Yong-Seok; Son, Hyeon

doi:10.1016/j.neuropharm.2008.09.019

Cited by 152 publications

(118 citation statements)

References 18 publications

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“…However, VPA activation of Neurod1 in adult hippocampal progenitors, like Egr1 activation in our adult SVZ NSCs, is independent of MAPK-ERK pathway activation [14]. In the case of Neurod1, transcriptional activation of pro-neural basic helix-loophelix transcription factors upstream of Neurod1 [23] could account for Neurod1 up-regulation. Chromatin immunoprecipitation data from our laboratory (unpublished) indicates VPA indirectly activates Egr1.…”

mentioning

confidence: 79%

“…These include mitogen activated protein kinase (MAPK) signaling [12,16], glycogen synthase kinase-3 (GSK-3) activity [5] and inositol and phospholipid signaling [4,22]. Furthermore, at high doses VPA inhibits histone deacetylase (HDAC) activity [11] and HDACmediated responses are proposed to contribute to the differential neurogenic effects of VPA in the normal and epileptic adult rodent brain [14,15,23].…”

mentioning

confidence: 99%

“…NSCs from the adult SVZ were grown in proliferating culture conditions with 1 mM VPA for 2-7 days (1 mM VPA has been shown to inhibit the proliferation of hippocampal progenitor cells and promote neurogenesis in culture, see [14,23]). VPA-treated adult NSCs produce fewer neurospheres of comparable size or density when compared to vehicle-treated controls (Fig.…”

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confidence: 99%

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Valproic acid inhibits neurosphere formation by adult subventricular cells by a lithium-sensitive mechanism

Zhou

Dalgard

Wynder

et al. 2011

Neuroscience Letters

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confidence: 79%

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confidence: 99%

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Valproic acid inhibits neurosphere formation by adult subventricular cells by a lithium-sensitive mechanism

Zhou

Dalgard

Wynder

et al. 2011

Neuroscience Letters

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“…Furthermore, VPA promotes neuronal differentiation from progenitor stages (Hsieh et al, 2004;Yu et al, 2009) and the drug induces in cell culture and brain the upregulation of open chromatinassociated histone acetylation and methylation markings at promoters of genes with a key role in neurotransmission (Gavin et al, 2009;Guidotti et al, 2009;Huang et al, 2007b). It will be interesting to quantify these VPA-dependent effects on pluripotency and neuronal differentiation, and to compare VPA treatment responders to non-responders.…”

Section: Psychiatric Epigenetics In the Culture Dish?mentioning

confidence: 99%

Epigenetics in the Human Brain

Houston

Peter

Mitchell

et al. 2012

Neuropsychopharmacol

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Many cellular constituents in the human brain permanently exit from the cell cycle during pre-or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether 4100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size.

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“…BDNF has been shown to be required for striatal neuron survival [10]. Similar to BDNF, the histone deacetylase inhibitor valproic acid (VPA) is also used frequently in differentiation protocols [16,17] and was shown to inhibit neural progenitor cell (NPC) proliferation and to introduce neuronal differentiation [20]. Neuronal differentiation is also triggered by a dibutyryl-cAMP-induced nuclear accumulation of fibroblast growth factor receptor-1 [21] and by insulin-like growth factor 1 (Igf-1) [22].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons

Lin

Yuan

Sander

et al. 2015

Stem Cells Translational Medicine

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Huntington's disease (HD) results from a CAG repeat expansion in the gene encoding the huntingtin protein. This inherited disorder is characterized by progressive neurodegeneration. In particular, HD progression involves the loss of striatal projection neurons. The limited availability of reliable sources of human striatal projection neurons currently hampers our understanding of HD mechanisms and hinders the development of novel HD treatments. In this paper, we described two-and three-step methods for differentiating human neural progenitor cells toward striatal projection neurons. In the two-step differentiation protocol, 90%, 54%, and 6% of MAP2-positive cells were immunopositive for GABA, calbindin (CALB1), and DARPP-32/PPP1R1B, respectively. In the three-step differentiation protocol, 96%, 84%, and 21% of MAP2-positive cells were immunopositive for GABA, calbindin, and DARPP-32/PPP1R1B, respectively. In line with a striatal projection neuron phenotype, cells differentiated with our protocols displayed significantly increased expression of MAP2, CALB1, DARPP-32/PPP1R1B, ARPP21, and CTIP2. Application of glutamate receptor agonists induced calcium influx; accordingly, the cells also expressed various ionotropic glutamate receptor subunits. Differentiated cells also released GABA on stimulation. We suggest that our three-step differentiation protocol presents a reliable and simplified method for the generation of striatal projection neurons, yielding a critical resource for neuronal physiology and neurodegenerative disorder studies. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:775-788 SIGNIFICANCEThe earliest changes in the neurodegenerative disorder Huntington's disease affect a specific type of brain neurons, the so-called medium spiny neurons of the striatum. In this study, two protocols were developed for the differentiation of neural progenitor cells into striatal medium spiny neurons, and the differentiated neurons were extensively characterized. The data indicate that the three-step differentiation protocol presents a reliable and simplified method for the generation of striatal medium spiny neurons. The generated striatal medium spiny neurons could represent a critical resource for the study of neurodegenerative disorders, a model system for drug discovery, and a step toward cellbased regeneration therapies.

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Valproic acid promotes neuronal differentiation by induction of proneural factors in association with H4 acetylation

Cited by 152 publications

References 18 publications

Valproic acid inhibits neurosphere formation by adult subventricular cells by a lithium-sensitive mechanism

Valproic acid inhibits neurosphere formation by adult subventricular cells by a lithium-sensitive mechanism

Epigenetics in the Human Brain

In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons

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