Aging alters the molecular dynamics of synapses in a sexually dimorphic pattern in zebrafish (Danio rerio)

Neurobiol Aging. 2017 Jun:54:10-21. doi: 10.1016/j.neurobiolaging.2017.02.007. Epub 2017 Feb 20.

Abstract

The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.

Keywords: Aging; Excitatory synapses; Gender; Inhibitory synapses; Synaptic proteins; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging* / genetics
  • Analysis of Variance
  • Animals
  • Brain / metabolism*
  • Brain / physiology*
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism
  • Female
  • Humans
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism
  • Models, Animal
  • SAP90-PSD95 Associated Proteins / analysis
  • SAP90-PSD95 Associated Proteins / metabolism*
  • Sex Characteristics*
  • Synapses / genetics*
  • Synapses / metabolism
  • Synapses / physiology*
  • Synaptophysin / analysis
  • Synaptophysin / metabolism*
  • Zebrafish

Substances

  • Carrier Proteins
  • Membrane Proteins
  • SAP90-PSD95 Associated Proteins
  • Synaptophysin
  • gephyrin