Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain.
Department of Animal Pathology, University of Zaragoza, Zaragoza, Spain.
Sci Rep. 2020 Sep 17;10(1):15240. doi: 10.1038/s41598-020-71905-y.
Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.
氢氧化铝佐剂对牲畜和人类疫苗至关重要。很少有研究分析它们在体内对中枢神经系统的影响。在这项工作中,羔羊在 16 个月内接受了三种不同的处理,即皮下平行接种含铝的商业疫苗、等量的氢氧化铝或模拟注射。通过 RNA-seq 和 miRNA-seq 对脑样本进行测序,以分析 mRNA、长非编码 RNA 和 microRNA 的表达,并进行了三次表达比较。尽管只鉴定出少数差异表达的基因,但一些由氢氧化铝单独调节的失调基因与神经功能有关,其中包括 lncRNA TUNA,或与线粒体能量代谢相关功能富集。同样,miRNA 的表达主要被佐剂单独处理所扰乱。一些差异表达的 miRNA 先前与神经疾病、氧化应激和细胞凋亡有关。简而言之,在这项研究中,氢氧化铝单独处理比温和的商业疫苗更能改变大脑的转录组。接种氢氧化铝的动物的表达变化表明线粒体功能障碍。需要进一步的研究来阐明这些变化在多大程度上可能具有病理后果。