Glycolysis mediates neuron specific histone acetylation in valproic acid-induced human excitatory neuron differentiation

Chen, Andi; Wang, Mengmeng; Xu, Chao; Zhao, Yumin; Xian, Panpan; Li, Yuqian; Zheng, Weian; Yi, Xuyang; Wu, Shengxi; Wang, Shaobin

doi:10.3389/fnmol.2023.1151162

Cited by 6 publications

(1 citation statement)

References 36 publications

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“…In addition, studies in vitro have helped us understand VPA’s effects on neurogenesis and cell growth. Exposure to 1mM VPA decreases the proliferation of human NPCs in culture, followed by mitochondrial dysfunction and increased differentiation to an excitatory neuronal phenotype [ 234 ]. Interestingly, NPCs from rat embryos exposed to 0.5 mM VPA increase proliferation and differentiation to a neuronal phenotype [ 222 ], suggesting different effects according to the VPA concentration.…”

Section: Vpa and Disruption Of Brain Developmentmentioning

confidence: 99%

Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder

Zarate-Lopez,

Torres-Chávez,

Gálvez-Contreras

et al. 2024

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increased prevalence and incidence in recent decades. Its etiology remains largely unclear, but it seems to involve a strong genetic component and environmental factors that, in turn, induce epigenetic changes during embryonic and postnatal brain development. In recent decades, clinical studies have shown that inutero exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug, is an environmental factor associated with an increased risk of ASD. Subsequently, prenatal VPA exposure in rodents has been established as a reliable translational model to study the pathophysiology of ASD, which has helped demonstrate neurobiological changes in rodents, non-human primates, and brain organoids from human pluripotent stem cells. This evidence supports the notion that prenatal VPA exposure is a valid and current model to replicate an idiopathic ASD-like disorder in experimental animals. This review summarizes and describes the current features reported with this animal model of autism and the main neurobiological findings and correlates that help elucidate the pathophysiology of ASD. Finally, we discuss the general framework of the VPA model in comparison to other environmental and genetic ASD models.

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Section: Vpa and Disruption Of Brain Developmentmentioning

confidence: 99%

Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder

Zarate-Lopez,

Torres-Chávez,

Gálvez-Contreras

et al. 2024

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Epigenetic underpinnings of the autistic mind: Histone modifications and prefrontal excitation/inhibition imbalance

Fard,

Sadeghi,

Pajoohesh

et al. 2024

American J of Med Genetics Pt B

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Autism spectrum disorder (ASD) is complex neurobehavioral condition influenced by several cellular and molecular mechanisms that are often concerned with synaptogenesis and synaptic activity. Based on the excitation/inhibition (E/I) imbalance theory, ASD could be the result of disruption in excitatory and inhibitory synaptic transmission across the brain. The prefrontal cortex (PFC) is the chief regulator of executive function and can be affected by altered neuronal excitation and inhibition in the course of ASD. The molecular mechanisms involved in E/I imbalance are subject to epigenetic regulation. In ASD, altered enrichment and spreading of histone H3 and H4 modifications such as the activation‐linked H3K4me2/3, H3K9ac, and H3K27ac, and repression‐linked H3K9me2, H3K27me3, and H4K20me2 in the PFC result in dysregulation of molecules mediating synaptic excitation (ARC, EGR1, mGluR2, mGluR3, GluN2A, and GluN2B) and synaptic inhibition (BSN, EphA7, SLC6A1). Histone modifications are a dynamic component of the epigenetic regulatory elements with a pronounced effect on patterns of gene expression with regards to any biological process. The excitation/inhibition imbalance associated with ASD is based on the excitatory and inhibitory synaptic activity in different regions of the brain, including the PFC, the ultimate outcome of which is highly influenced by transcriptional activity of relevant genes.

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Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation

Sánchez-Ramírez,

Ung,

Stringari

et al. 2024

Mol Neurobiol

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Stem cells possess extraordinary capacities for self-renewal and differentiation, making them highly valuable in regenerative medicine. Among these, neural stem cells (NSCs) play a fundamental role in neural development and repair processes. NSC characteristics and fate are intricately regulated by the microenvironment and intracellular signaling. Interestingly, metabolism plays a pivotal role in orchestrating the epigenome dynamics during neural differentiation, facilitating the transition from undifferentiated NSC to specialized neuronal and glial cell types. This intricate interplay between metabolism and the epigenome is essential for precisely regulating gene expression patterns and ensuring proper neural development. This review highlights the mechanisms behind metabolic regulation of NSC fate and their connections with epigenetic regulation to shape transcriptional programs of stemness and neural differentiation. A comprehensive understanding of these molecular gears appears fundamental for translational applications in regenerative medicine and personalized therapies for neurological conditions.

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Glycolysis mediates neuron specific histone acetylation in valproic acid-induced human excitatory neuron differentiation

Cited by 6 publications

References 36 publications

Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder

Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder

Epigenetic underpinnings of the autistic mind: Histone modifications and prefrontal excitation/inhibition imbalance

Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation

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