Neocortical developmental analysis of vasculature and their growth factors offer new insight into fragile X syndrome abnormalities

Amogh P. Belagodu, Stephen Fleming, Roberto Galvez

Research output: Contribution to journalArticlepeer-review

Abstract

Fragile X Syndrome (FXS) is the most common single gene cause for Autism Spectrum Disorder and the most prevalent form of inherited mental retardation. Our prior studies have demonstrated that adult FXS mice have abnormal blood vessel density (BVD) and elevated Vascular Endothelial Growth Factor A expression (VEGF-A). VEGF-A is one of the most prominent regulators of BVD, and its abnormal expression is the most likely cause for FXS BVD abnormalities. We have demonstrated that attenuating elevated VEGF-A expression can ameliorate many non-vascular FXS abnormalities (Belagodu, Zendeli Slater and Galvez: Dev Neurobiol 77 (2017) 14–25), suggesting that abnormal VEGF-A expression is an underlying cause for some FXS abnormalities. However, FXS is a developmental disorder and VEGF-A's potential role in mediating FXS abnormalities during development have never been explored. Furthermore, VEGF-A is one protein in a family of proteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D, & PLGF) that activate one of three primary receptors (VEGFR1, VEGFR2, & VEGFR3). Abnormal expression of any of these proteins could hinder proper development. The current study demonstrated that FXS mice do not exhibit normal BVD developmental patterns, resulting in elevated adult expression, most likely due to observed elevated VEGF-A adult expression. Interestingly, all five VEGF family of proteins exhibited altered developmental expression patterns that could cause abnormal development. However, none of the receptors exhibited abnormal adult expression, but did exhibit altered developmental expression. Expanding upon our prior analyses, the current study provides additional interesting insight towards potential developmental mechanisms mediating FXS abnormalities, while offering further sites for age specific therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)1321-1333
Number of pages13
JournalDevelopmental Neurobiology
Volume77
Issue number11
DOIs
StatePublished - Nov 2017

Keywords

  • Autism
  • FMRP
  • VEGF
  • development
  • vascularization

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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