Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice

Mol Neurobiol. 2024 Nov;61(11):8575-8589. doi: 10.1007/s12035-024-04066-y. Epub 2024 Mar 25.

Abstract

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy.

Keywords: Alzheimer's disease; Circ-Bptf; Learning and memory; miR-138-5p; p62.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Dendritic Spines / metabolism
  • Dendritic Spines / pathology
  • Hippocampus / metabolism
  • Learning / physiology
  • Male
  • Memory Disorders* / genetics
  • Memory Disorders* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • MicroRNAs
  • MIRN138 microRNA, mouse
  • Presenilin-1
  • RNA, Circular
  • Transcription Factors