A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain

J Neurosci Res. 2018 Feb;96(2):180-193. doi: 10.1002/jnr.24082. Epub 2017 May 16.

Abstract

Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes.

Keywords: AQP4; SCR_003302; SCR_008083; SCR_010943; astrocytes; dystrophin-associated complex; glymphatic; perivascular endfoot.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Aquaporin 4 / metabolism
  • Astrocytes / metabolism*
  • Brain / cytology*
  • Brain / growth & development*
  • Calcium-Binding Proteins / metabolism
  • Child
  • Dystrophin-Associated Protein Complex / metabolism*
  • Dystrophin-Associated Proteins / metabolism
  • Female
  • Gene Ontology
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Muscle Proteins / metabolism
  • Neuropeptides / metabolism
  • Subcellular Fractions / metabolism
  • Transcriptome / physiology*
  • Young Adult

Substances

  • Aquaporin 4
  • Calcium-Binding Proteins
  • DTNA protein, human
  • Dystrophin-Associated Protein Complex
  • Dystrophin-Associated Proteins
  • Membrane Proteins
  • Muscle Proteins
  • Neuropeptides
  • syntrophin alpha1