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类神经组织样而非超生理电导率通过钙信号和表观遗传修饰来刺激神经元谱系特化。

Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.

机构信息

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Chungcheongnam-do, 31116, Republic of Korea.

出版信息

Adv Sci (Weinh). 2024 Sep;11(35):e2400586. doi: 10.1002/advs.202400586. Epub 2024 Jul 10.

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, 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) 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). 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一个重要生物物理因素,但由于难以孤立地分离出这一线索,最佳值仍存在争议。为了解决这个问题,设计了由碳纳米管和氧化石墨烯纳米带制成的导电基底,其电导率范围从 0.02 到 3.2 S m,同时控制其他表面特性。重点是确定电导率的变化是否对神经谱系特化有任何明显的影响。值得注意的是,与高超生理电导率(3.2 S m)相比,神经组织样低电导率(0.02-0.1 S m)促使神经干细胞/祖细胞表现出更大的神经元谱系特化倾向(神经元和少突胶质细胞,而不是星形胶质细胞)。高电导率引发了细胞凋亡过程,表现为凋亡分数增加和神经发生形态特征减少,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,特别是 H3 乙酰化(H3ac)和神经发生转录因子激活增加的染色质开放性,以及更平衡的细胞内钙反应。H3ac 的药理学抑制进一步支持了这样的观点,即这种表观遗传变化可能在响应神经组织样而不是超生理的导电线索驱动神经元特化中发挥关键作用。这些发现强调了在设计神经接口和支架以刺激神经元分化和促进修复过程时,最佳电导率的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c62/11425260/b7d37431df18/ADVS-11-2400586-g001.jpg

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