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Comparative analysis of the down syndrome hippocampal non-coding RNA transcriptomes using a mouse model.

Zhaowei Cai1, Zhilan Xiao2, Yufang Wang2

  • 1Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.

Genes & Genomics
|September 18, 2020
PubMed
Summary

This study maps dysregulated non-coding RNAs (ncRNAs) in Down syndrome (DS) hippocampus, revealing significant changes in microRNAs, long non-coding RNAs, and circular RNAs. These findings offer insights into DS-related cognitive deficits.

Keywords:
Circular RNADown syndromeHippocampusTranscriptomelncRNAmicroRNA

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Down syndrome (DS), a chromosomal disorder from trisomy 21, is linked to hippocampal abnormalities causing cognitive deficits.
  • Non-coding RNAs (ncRNAs) are crucial for brain development and function, but their role in DS remains largely unknown.
  • Investigating dysregulated ncRNAs in DS is essential for understanding its pathology.

Purpose of the Study:

  • To create a comprehensive map of dysregulated ncRNAs, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the DS hippocampus.
  • To utilize DS mouse models for further mechanistic and therapeutic studies.

Main Methods:

  • Employed the Dp(16)1/Yey DS mouse model, which carries trisomy for the human chromosome 21 syntenic region.
  • Isolated hippocampi from seven-day-old pups for library construction and next-generation sequencing.
  • Analyzed differentially expressed miRNAs, lncRNAs, and circRNAs.

Main Results:

  • Identified differentially expressed (DE) miRNAs, lncRNAs, and circRNAs in the DS hippocampus.
  • Observed limited regulatory interactions between DE miRNAs and DE messenger RNAs (mRNAs).
  • Found significant alterations in circRNAs, with host genes enriched in functions impaired in DS, such as synaptic plasticity and neurotransmission.

Conclusions:

  • Generated the first transcriptome map of ncRNAs in the developing DS hippocampus.
  • This foundational work paves the way for future research into the role of ncRNAs in hippocampal function and DS pathology.