Zebrafish brain RNA sequencing reveals that cell adhesion molecules are critical in brain aging

Neurobiol Aging. 2020 Oct:94:164-175. doi: 10.1016/j.neurobiolaging.2020.04.017. Epub 2020 May 12.

Abstract

Brain aging is a complex process, which involves multiple pathways including various components from cellular to molecular. This study aimed to investigate the gene expression changes in zebrafish brains through young-adult to adult, and adult to old age. RNA sequencing was performed on isolated neuronal cells from zebrafish brains. The cells were enriched in progenitor cell markers, which are known to diminish throughout the aging process. We found 176 statistically significant, differentially expressed genes among the groups, and identified a group of genes based on gene ontology descriptions, which were classified as cell adhesion molecules. The relevance of these genes was further tested in another set of zebrafish brains, human healthy, and Alzheimer's disease brain samples, as well as in Allen Brain Atlas data. We observed that the expression change of 2 genes, GJC2 and ALCAM, during the aging process was consistent in all experimental sets. Our findings provide a new set of markers for healthy brain aging and suggest new targets for therapeutic approaches to neurodegenerative diseases.

Keywords: Brain aging; Cell adhesion molecules; RNA sequencing; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / genetics
  • Activated-Leukocyte Cell Adhesion Molecule / metabolism
  • Aging / genetics*
  • Aging / metabolism*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Brain / metabolism*
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Connexins / genetics
  • Fetal Proteins / genetics
  • Fetal Proteins / metabolism
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • RNA / genetics*
  • RNA / metabolism*
  • Sequence Analysis, RNA / methods*
  • Zebrafish

Substances

  • ALCAM protein, human
  • Activated-Leukocyte Cell Adhesion Molecule
  • Antigens, CD
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Connexins
  • Fetal Proteins
  • connexin 47
  • RNA