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

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.

Activity Dependency and Aging in the Regulation of Adult Neurogenesis

“…Neurotrophic factors, growth factors, and their receptors are abundant during development and decline with age (Wise 2003;Shetty et al 2005;Chadashvili and Peterson 2006). Growth factors have a strong influence on precursor cell proliferation and neuronal differentiation and, thus, might be important mediators of cellular plasticity in aging (Cameron et al 1998;Kwon 2002;Hattiangady et al 2005;Shetty et al 2005).…”

“…Fibroblast growth factor 2 (FGF-2), which is necessary to grow hippocampal precursor cells in vitro (Palmer et al 1995), is another key candidate for mediating activity-dependent effects across the life span (Jin et al 2003), because FGF-2 can act systemically (Wagner et al 1999), is proneurogenic in the adult brain (Kuhn et al 1997), declines with age , is up-regulated in activity paradigms (BickSander et al 2006), and FGF-2 receptor expression is prominent in the neurogenic zones of the adult and aged rodent brain (Chadashvili and Peterson 2006).…”

Acute Psychosocial Stress Reduces Cell Survival in Adult Hippocampal Neurogenesis without Altering Proliferation

“…The absence of glucocorticoid receptors in newly generated cells (Cameron et al, 1998;Mirescu et al, 2004), or their expression in a small percentage of proliferating cells (Garcia et al, 2004), is consistent with this interpretation. The observation that the number of new cells expressing glucocorticoid receptors increases by 4 d after their generation (Garcia et al, 2004) indicates that any direct effect of elevated CORT is delayed until after their generation, possibly contributing to reduced cell survival; however, glucocorticoid receptors are present on astrocytes in the hippocampus, suggesting that CORT influence may actually be indirect, secondary to activation of regional astrocytes (Song et al, 2002;Chadashvili and Peterson, 2006). Together, these observations suggest that acute psychosocial stress may impact neurogenesis indirectly by shifting the expression of regulatory factors within the environmental niche of the hippocampus (Wong and Herbert, 2005), with possible direct effects not contributing until several days after proliferation.…”

Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate‐induced injury is lost by middle age

“…Studies on neurogenesis during normal aging demonstrate that the number of NSCs remains stable during the course of aging but NSCs in the middle-aged and aged hippocampus exhibit dramatically diminished proliferation (Rao et al ., 2006a;Tang et al ., 2007;Hattiangady & Shetty, 2008). This is likely because of changes in their microenvironment such as the reduced concentration of NSC mitogenic factors BDNF, FGF-2, IGF-1, and VEGF Shetty et al ., 2005a), changes in the relationship between vascular niches and NSCs (Hattiangady & Shetty, 2008) and alterations in receptors mediating the actions of mitogenic factors (Chadashvili & Peterson, 2006). Moreover, studies on post-lesion plasticity indicate that aging considerably diminishes the synaptic reorganization that occurs in response to injury in the hippocampus.…”