Genetic Features of Young and Aged Animals After Peripheral Nerve Injury: Implications for Diminished Regeneration Capacity.

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-11-03 DOI:10.1007/s10571-023-01431-8
Weixiao Huang, Sheng Yi, Lili Zhao
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引用次数: 0

Abstract

The spontaneous regeneration capacity of peripheral nerves is fundamentally reduced with advancing age, leading to severe and long-term functional loss. The cellular and molecular basis underlying incomplete and delayed recovery of aging peripheral nerves is still murky. Here, we collected sciatic nerves of aged rats at 1d, 4d, and 7d after nerve injury, systematically analyzed the transcriptional changes of injured sciatic nerves, and examined the differences of injury responses between aged rats and young rats. RNA sequencing revealed that sciatic nerves of aged and young rats exhibit distinctive expression patterns after nerve injury. Acute and vigorous immune responses, including motivated B cell receptor signaling pathway, occurred in injured sciatic nerves of both aged and young rats. Different from young rats, aged rats have more CD8+ T cells and B cells in normal state and the elevation of M2 macrophages seemed to be more robust in sciatic nerves, especially at later time points after nerve injury. Young rats, on the other hand, showed strong and early up-regulation of cell cycle-related genes. These identified unique transcriptional signatures of aged and young rats help the understanding of aged-associated injury responses in the wound microenvironments and provide essential basis for the treatment of regeneration deficits in aged population.

Abstract Image

周围神经损伤后年轻和老年动物的遗传特征:再生能力下降的意义。
随着年龄的增长,外周神经的自发再生能力从根本上降低,导致严重和长期的功能丧失。衰老周围神经不完全和延迟恢复的细胞和分子基础仍然模糊不清。在这里,我们收集了神经损伤后1d、4d和7d的老年大鼠坐骨神经,系统分析了损伤坐骨神经的转录变化,并检测了老年大鼠和年轻大鼠损伤反应的差异。RNA测序显示,老年和年轻大鼠的坐骨神经在神经损伤后表现出不同的表达模式。在老年和年轻大鼠的坐骨神经损伤中都发生了急性和剧烈的免疫反应,包括活化的B细胞受体信号通路。与年轻大鼠不同,老年大鼠在正常状态下有更多的CD8+T细胞和B细胞,坐骨神经中M2巨噬细胞的升高似乎更为强烈,尤其是在神经损伤后的后期。另一方面,年轻大鼠表现出对细胞周期相关基因的强烈和早期上调。这些确定的老年和年轻大鼠独特的转录特征有助于理解创伤微环境中与衰老相关的损伤反应,并为治疗老年群体的再生缺陷提供重要基础。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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