Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, 32-083, Balice, Kraków, Poland.
Center for Experimental and Innovative Medicine, University of Agriculture in Kraków, Rędzina 1c, 30-248, Kraków, Poland.
Biol Sex Differ. 2020 Dec 11;11(1):67. doi: 10.1186/s13293-020-00343-2.
MicroRNAs indirectly orchestrate myriads of essential biological processes. A wide diversity of miRNAs of the neurodevelopmental importance characterizes the brain tissue, which, however, exhibits region-specific miRNA profile differences. One of the most conservative regions of the brain is periaqueductal grey (PAG) playing vital roles in significant functions of this organ, also those observed to be sex-influenced. The domestic pig is an important livestock species but is also believed to be an excellent human model. This is of particular importance for neurological research because of the similarity of pig and human brains as well as difficult access to human samples. However, the pig PAG profile has not been characterized so far. Moreover, molecular bases of sex differences connected with brain functioning, including miRNA expression profiles, have not been fully deciphered yet.
Thus, in this study, we applied next-generation sequencing to characterize pig PAG expressed microRNAs. Furthermore, we performed differential expression analysis between females and males to identify changes of the miRNA profile and reveal candidates underlying sex-related differences.
As a result, known brain-enriched, and new miRNAs which will expand the available profile, were identified. The downstream analysis revealed 38 miRNAs being differentially expressed (DE) between female and male samples. Subsequent pathway analysis showed that they enrich processes vital for neuron growth and functioning, such as long-term depression and axon guidance. Among the identified sex-influenced miRNAs were also those associated with the PAG physiology and diseases related to this region.
The obtained results broaden the knowledge on the porcine PAG miRNAome, along with its dynamism reflected in different isomiR signatures. Moreover, they indicate possible mechanisms associated with sex-influenced differences mediated via miRNAs in the PAG functioning. They also provide candidate miRNAs for further research concerning, i.e., sex-related bases of physiological and pathological processes occurring in the nervous system.
微小 RNA 间接协调着无数重要的生物学过程。神经发育相关的 miRNA 种类繁多，特征在于脑组织具有区域特异性 miRNA 谱差异。大脑中最保守的区域之一是脑桥被盖外侧区（periaqueductal grey，PAG），在该器官的重要功能中发挥着至关重要的作用，这些功能也受到性别影响。家猪是一种重要的家畜物种，但也被认为是人类的良好模型。这一点尤其重要，因为猪和人类的大脑非常相似，而且很难获得人类样本，所以这对于神经科学研究很重要。然而，猪的 PAG 图谱尚未得到描述。此外，与大脑功能相关的性别差异的分子基础，包括 miRNA 表达谱，尚未完全阐明。
因此，在这项研究中，我们应用下一代测序技术来描述猪 PAG 表达的 microRNA。此外，我们进行了雌性和雄性之间的差异表达分析，以识别 miRNA 谱的变化，并揭示潜在的性别相关差异的候选者。
结果鉴定出了已知的脑富集 miRNA 和新的 miRNA，这将扩展可用的 miRNA 图谱。下游分析显示 38 个 miRNA 在雌性和雄性样本之间存在差异表达。随后的通路分析表明，它们富集了对神经元生长和功能至关重要的过程，如长时程抑制和轴突导向。在所鉴定的性别影响 miRNA 中，还有一些与 PAG 生理学以及与该区域相关的疾病有关。
这些结果拓宽了对猪 PAG miRNAome 的认识，以及反映在不同的 isomiR 特征中的动态变化。此外，它们表明了与 PAG 功能中的性别影响差异相关的可能机制，这些差异是通过 miRNA 介导的。它们还为进一步研究提供了候选 miRNA，例如与神经系统中发生的生理和病理过程的性别相关基础有关的研究。
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