LncRNAs down-regulate Myh1, Casr, and Mis18a expression in the Substantia Nigra of aged male rats.

Guoliang Zhang,Yunxiao Kang,Shufeng Liu,Yannan Ma,Rui Cui,Xu Feng,Geming Shi,Yuanxiang Huang,Xiaoming Ji,Qiqing Guo

doi:10.18632/aging.102321

Abstract

In this study, we used high-throughput RNA sequencing to identify mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are differentially expressed in the Substantia Nigra (SN) of aged and young rats. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to perform functional annotation of mRNAs that were either differentially expressed themselves (DEMs), targeted by differentially expressed lncRNAs (DELs), or the parents of differentially expressed circRNAs (DECs). A total of 112 DEMs, 163 DELs, and 98 DECs were found in the SN of aged rats. The down-regulated lncRNA NONRATT010417.2 targeted the down-regulated mRNA Myh1, while the down-regulated lncRNA NONRATT015586.2 and the up-regulated lncRNAs NONRATT000490.2 and NONRATT007029.2 all targeted the down-regulated mRNAs Casr and Mis18a. Western blots and RT-qPCR revealed that Myh1, Casr, and Mis18a protein and mRNA expression were significantly reduced in aged rats compared to young rats. This study improves our understanding of the transcriptional alterations underlying aging-related changes in the SN and provides a foundation for future studies of associated molecular mechanisms.

Highlights

Aging is associated with the accumulation of deficits in cognition and motor control and with increased risk of neurodegenerative diseases, such as Parkinson’s disease [1,2,3]
We identified Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with the differentially expressed messenger RNAs (mRNAs) (DEMs), the mRNAs targeted by differentially expressed long non-coding RNAs (lncRNAs) (DELs), and the parental mRNAs of the differentially expressed circRNAs (DECs)
We identified a total of 112 mRNAs that are differentially expressed in the Substantia Nigra (SN) of 24- and sixmonth old rats

Summary

Introduction

Aging is associated with the accumulation of deficits in cognition and motor control and with increased risk of neurodegenerative diseases, such as Parkinson’s disease [1,2,3]. The dopaminergic neurons of the SN are vulnerable to age-related degenerative processes [5]. The number and dopamine content of dopaminergic neurons in the SN progressively decreases, which leads to aging-related behavioral deficits [6, 7]. The dopaminergic neurons of the SN are vulnerable to oxidative stress [8] and inflammatory attack [9]. Reduced dopamine activity during normal aging is linked to age-related mitochondrial DNA damage [10]. The mechanisms responsible for dysfunction and degeneration of the SN dopamine www.aging-us.com neurons in normal aging are complex and are not yet fully understood

Methods

Results

Conclusion