Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disease with a high incidence worldwide, and with no medications currently able to prevent the progression of AD. Danggui-Shaoyao-San (DSS) is widely used in traditional Chinese medicine (TCM) and has been proven to be effective for memory and cognitive dysfunction, yet its precise mechanism remains to be delineated. The present study was designed to investigate the genome-wide expression profile of long non-coding RNAs (LncRNAs) and messenger RNAs (mRNAs) in the hippocampus of APP/PS1 mice after DSS treatment by RNA sequencing. A total of 285 differentially expressed LncRNAs and 137 differentially expressed mRNAs were identified (fold-change ≥2.0 and P < 0.05). Partial differentially expressed LncRNAs and mRNAs were selected to verify the RNA sequencing results by quantitative polymerase chain reaction (qPCR). A co-expression network was established to analyze co-expressed LncRNAs and genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to evaluate the biological functions related to the differentially co-expressed LncRNAs, and the results showed that the co-expressed LncRNAs were mainly involved in AD development from distinct origins, such as APP processing, neuron migration, and synaptic transmission. Our research describes the lncRNA and mRNA expression profiles and functional networks involved in the therapeutic effect of DSS in APP/PS1 mice model. The results suggest that the therapeutic effect of DSS on AD involves the expression of LncRNAs. Our findings provide a new perspective for research on the treatment of complex diseases using traditional Chinese medicine prescriptions.

Highlights

  • Alzheimer’s disease (AD), the most common type of dementia in aging populations, has a complicated etiology, involves several nervous dysfunctions, and represents a challenge in health care systems [1]

  • AD is a complex disease caused by multiple pathways; the treatment principle of monotherapy acting on a single target is not appropriate

  • We investigated the differences in long non-coding RNAs (LncRNAs) and messenger RNAs (mRNAs) expression in the hippocampus of APP/PS1 double transgenic mice treated with DSS or untreated, using RNA sequencing, and LncRNA and mRNA co-expression networks were constructed

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Summary

Introduction

Alzheimer’s disease (AD), the most common type of dementia in aging populations, has a complicated etiology, involves several nervous dysfunctions, and represents a challenge in health care systems [1]. Many drugs have been developed to treat AD, none slows or prevents the progression of AD [3]. AD is a complex disease caused by multiple pathways; the treatment principle of monotherapy acting on a single target is not appropriate. The holistic view of traditional Chinese medicine (TCM) regarding the treatment of multiple components and multiple targets provides a bright prospect for the prevention and treatment of AD [4]. A TCM formulation (prescription or fangji in Chinese) Danggui-Shaoyao-San (DSS), called Dangguijakyak-san or Toki-shakuyaku-san in Japanese, has been used for neurodegenerative diseases in China for more than 2,000 years. A large amount of evidence supports the therapeutic effect of www.aging-us.com

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