关键词: calcium signaling electrical conductivity epigenetic change neural lineage specification

来  源:   DOI:10.1002/advs.202400586

Abstract:
Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.
摘要:
电导率是神经界面的关键生物物理因素,尽管由于隔离这一线索的挑战,最优值仍然存在争议。为了解决这个问题,由碳纳米管和氧化石墨烯纳米带制成的导电基板,表现出0.02至3.2Sm-1的电导率光谱,同时控制其他表面性能。重点是确定孤立变化的电导率是否对神经谱系规格有任何可辨别的影响。值得注意的是,神经组织样低电导率(0.02-0.1Sm-1)促使神经干/祖细胞表现出对神经元谱系规范的更大倾向(神经元和少突胶质细胞,不是星形胶质细胞)与高的超生理电导率(3.2Sm-1)相比。高电导率引发了凋亡过程,以凋亡分数增加和神经源性形态学特征减少为特征,主要是由于钙超载。相反,暴露于生理电导率的细胞表现出表观遗传变化,特定增加的染色质开放性与H3乙酰化(H3ac)和神经源性转录因子激活,以及更平衡的细胞内钙反应。H3ac的药理抑制作用进一步支持了这样的观点,即这种表观遗传变化可能在驱动神经元对神经组织样的反应中起关键作用,不是超生理,导电线索。这些发现强调了在设计神经界面和支架以刺激神经元分化并促进修复过程时最佳电导率的必要性。
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