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牛磺酸通过 Shh 介导的线粒体改善促进中风中的轴突发芽。

Taurine promotes axonal sprouting via Shh-mediated mitochondrial improvement in stroke.

机构信息

Capital Medical University - Beijing Chaoyang Hospital - Department of Neurosurgery - Beijing, China.

Second Hospital of Hebei Medical University - Department of Cardiology - Hebei, China.

出版信息

Acta Cir Bras. 2023 Jun 26;38:e382323. doi: 10.1590/acb382323. eCollection 2023.

DOI:10.1590/acb382323
PMID:37377249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10292808/
Abstract

PURPOSE

Motor function is restored by axonal sprouting in ischemic stroke. Mitochondria play a crucial role in axonal sprouting. Taurine (TAU) is known to protect the brain against experimental stroke, but its role in axonal sprouting and the underlying mechanism are unclear.

METHODS

We evaluated the motor function of stroke mice using the rotarod test on days 7, 14, and 28. Immunocytochemistry with biotinylated dextran amine was used to detect axonal sprouting. We observed neurite outgrowth and cell apoptosis in cortical neurons under oxygen and glucose deprivation (OGD), respectively. Furthermore, we evaluated the mitochondrial function, adenosine triphosphate (ATP), mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG-1α), transcription factor A of mitochondria (TFAM), protein patched homolog 1 (PTCH1), and cellular myelocytomatosis oncogene (c-Myc).

RESULTS

TAU recovered the motor function and promoted axonal sprouting in ischemic mice. TAU restored the neuritogenesis ability of cortical neurons and reduced OGD-induced cell apoptosis. TAU also reduced reactive oxygen species, stabilized mitochondrial membrane potential, enhanced ATP and mtDNA content, increased the levels of PGC-1α, and TFAM, and restored the impaired levels of PTCH1, and c-Myc. Furthermore, these TAU-related effects could be blocked using an Shh inhibitor (cyclopamine).

CONCLUSION

Taurine promoted axonal sprouting via Shh-mediated mitochondrial improvement in ischemic stroke.

摘要

目的

在缺血性中风中,轴突发芽恢复了运动功能。线粒体在轴突发芽中起着至关重要的作用。牛磺酸(TAU)已知可保护大脑免受实验性中风的影响,但它在轴突发芽中的作用及其潜在机制尚不清楚。

方法

我们使用旋转棒测试在第 7、14 和 28 天评估中风小鼠的运动功能。用生物素化葡聚糖胺进行免疫细胞化学染色,以检测轴突发芽。我们观察了皮质神经元在氧葡萄糖剥夺(OGD)下的神经突生长和细胞凋亡。此外,我们评估了线粒体功能、三磷酸腺苷(ATP)、线粒体 DNA(mtDNA)、过氧化物酶体增殖物激活受体γ共激活因子 1-α(PGC-1α)、线粒体转录因子 A(TFAM)、 patched 同源物 1(PTCH1)和细胞髓鞘细胞瘤癌基因(c-Myc)。

结果

TAU 恢复了缺血小鼠的运动功能并促进了轴突发芽。TAU 恢复了皮质神经元的神经发生能力,并减少了 OGD 诱导的细胞凋亡。TAU 还减少了活性氧,稳定了线粒体膜电位,增强了 ATP 和 mtDNA 含量,增加了 PGC-1α 和 TFAM 的水平,并恢复了受损的 PTCH1 和 c-Myc 水平。此外,这些与 TAU 相关的作用可以使用 Shh 抑制剂(环巴胺)阻断。

结论

牛磺酸通过 Shh 介导的线粒体改善促进了缺血性中风中的轴突发芽。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/6ab7308b9017/1678-2674-acb-38-e382323-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e94475dcf326/1678-2674-acb-38-e382323-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e7098b0af046/1678-2674-acb-38-e382323-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/34038d793886/1678-2674-acb-38-e382323-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/8c2b0ce00f9f/1678-2674-acb-38-e382323-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e636aaa345b8/1678-2674-acb-38-e382323-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e65fb3343365/1678-2674-acb-38-e382323-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/6ab7308b9017/1678-2674-acb-38-e382323-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e94475dcf326/1678-2674-acb-38-e382323-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e7098b0af046/1678-2674-acb-38-e382323-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/34038d793886/1678-2674-acb-38-e382323-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/8c2b0ce00f9f/1678-2674-acb-38-e382323-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e636aaa345b8/1678-2674-acb-38-e382323-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/e65fb3343365/1678-2674-acb-38-e382323-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/10292808/6ab7308b9017/1678-2674-acb-38-e382323-gf07.jpg

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