The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain

Abstract

Neurogenesis occurs in two regions of the adult brain, namely, the subventricular zone (SVZ) throughout the wall of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG) in hippocampal formation. Adult neurogenesis requires several neurotrophic factors to sustain and regulate the proliferation and differentiation of the adult stem cell population. In the present review, we examine the cellular and functional aspects of a trophic system mediated by fibroblast growth factor-2 (FGF-2) and its receptors (FGFRs) related to neurogenesis in the SVZ and SGZ of the adult rat brain. In the SVZ, FGF-2 is expressed in GFAP-positive cells of SVZ but is not present in proliferating precursor cells, which instead express FGFR-1 and FGFR-2, but not FGFR-3 mRNA, although expressed in the SVZ, and FGFR-4. Therefore, it seems that in the SVZ FGF-2 may be released by GFAP-positive cells, different from the precursor cell lineage, and via volume transmission it reaches the proliferating precursor cells. FGFR-1 mRNA is also expressed in the SGZ and is localized in BrdU-labeled precursor cells, whereas FGFR-2 and FGFR-3 mRNA, although expressed in the SGZ, are not located within proliferating precursor cells. An aged-related decline of proliferating precursor cells in the SVZ and DG of old rats has been well documented, and there is the suggestion that in part it could be the consequence of alterations in growth factor expression levels. Thus, the old precursors may respond to growth factors, suggesting that during aging the basic components for neuronal precursor cell proliferation are retained and the capacity to increase neurogenesis after appropriate stimulation is still preserved. In conclusion, the trophic system mediated by FGF-2 and its receptors contributes to create an important micro-environmental niche that promotes neurogenesis in the adult and aged brain.

α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors

“…Third, a2-tancytes respond to elevated levels of FGF in vivo through enhanced proliferation. FGFs and FGF receptors have been described in other adult NSC niches, and are widely accepted to be potent modulators of progenitor cell proliferation, but in neither the SVZ nor the SGZ do they display a highly localised distribution 44,45 . The presence of endogenous Fgfs and evidence of the requirement for active growth factor signalling suggest that FGF signalling has a role in the control of a-tanyctes under normal conditions, perhaps limiting differentiation that might occur through localised CNTF 1,46 .…”

The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

“…The most interesting observation was the significant difference in the mean dialysate concentration of FGF2 in the oldest patients compared with that of other age groups. This was an unexpected finding since FGF2 is generally thought as having an important role in recovery from brain damage (Monfils et al, 2005;Mudò et al, (2009;Yoshimura et al, 2001). However, based on data from experimental stroke models, it has been proposed that the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals.…”

Impact of diet on adult hippocampal neurogenesis

“…Over ten growth factors and neurotrophins have been found to influence AHN. Fibroblast growth factor (FGF-2) and epidermal growth factor (EGF) are the primary mitogens used in vitro to propagate neural progenitor cells, and FGF-2 is hypothesized to play a permissive role in vivo in hippocampal progenitor cell proliferation [82]. Indeed, it has been found that deletion of fibroblast growth factor receptor-1 in the CNS decreases hippocampal progenitor cell proliferation [127].…”