Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR-2) immunoreactivity in astrocytes of neurogenic and non-neurogenic regions of the young adult and aged rat brain

J Comp Neurol. 2006 Sep 1;498(1):1-15. doi: 10.1002/cne.21009.

Abstract

Fibroblast growth factors (FGFs) are polypeptides that exert diverse biological effects on many cell types and tissues during embryogenesis and adulthood. In the adult brain, FGF-2 is primarily expressed by astrocytes and select groups of neurons. It has been shown that FGF-2 is neuroprotective and can stimulate proliferation of NSCs in neurogenic regions of the adult mammalian brain. Cellular responses to FGFs are mediated through membrane-spanning tyrosine kinase receptors in conjunction with low affinity binding to heparin sulfate proteoglycans. Four FGF receptors (FGFR1-4) have been cloned and characterized to date. In this study, we describe the anatomical distribution of FGFR-2 in young and aged rat brains. We demonstrate that the olfactory bulb, hippocampus, and cerebellum display the most robust FGFR-2 expression and observed age-related decrease in FGFR-2 levels in some but not all brain regions. In addition, we identified astrocytes as the primary source of FGFR-2 expression using immunofluorescence confocal microscopy. The astrocyte populations in the neurogenic areas, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus, express high levels of FGFR-2 protein, which points to its possible involvement in neurogenesis. We also explored the role of FGFR-2 in response to perforant pathway lesion and observed enhanced FGFR-2 expression by astrocytes surrounding the lesion. Thus, FGF-2 biological effects on astrocytes appear to be mediated through FGFR-2-dependent mechanisms, and this may provide an indirect route by which FGF-2 acts on neuronal populations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Brain / cytology
  • Brain / growth & development*
  • Brain / metabolism*
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Down-Regulation / physiology
  • Female
  • Fibroblast Growth Factor 2 / metabolism*
  • Immunohistochemistry
  • Nerve Regeneration / physiology
  • Neuronal Plasticity / physiology
  • Perforant Pathway / injuries
  • Perforant Pathway / physiology
  • Rats
  • Rats, Inbred F344
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Up-Regulation / physiology

Substances

  • Fibroblast Growth Factor 2
  • Receptor, Fibroblast Growth Factor, Type 2