Basic fibroblast growth factor (FGF-2) participates in development, stimulates regeneration, and maintains vitality of neural cells. Interactions between growth factors and extracellular matrix (ECM) components may be critical to regulate astrocytic proliferation/reactivity and neuronal resilience following insult or disease. Indeed, new evidence indicates that specific heparan sulfate proteoglycans (HSPGs) present in the ECM act as signal transduction co- receptors for FGF-2. Therefore, it is likely that HSPGs have a critical role in the regulation of the action of the FGF-2 system on astrocyte proliferation and reactivity, and in turn, brain plasticity. The expression and function of astrocytes is altered in aging, predisposing the brain to lose its homeostasis. To better understand how changes in astrocyte function affect brain plasticity in aging, it is fundamental to examine how aging impacts molecular systems that control astrocyte function. It is likely that the integrated actions of FGF-2 and HSPGs play a key role in controlling astrocyte function throughout lifespan of the brain. We would like to examine the possibility that changes in astrocyte function in aging are associated with changes in the expression and function of FGF-2 and select HSPGs. It has been assumed that extracellular matrix proteoglycans solely provide an """"""""inactive"""""""" suitable media for neurite outgrowth. In contrast, we propose the idea that changes in proteoglycans in the aged brain may affect FGF-2 function, and in turn, plasticity of astrocytes and neurons. The elucidation of this mechanism could provide a new dimension of therapeutical approaches to enhance astrocyte function and neuronal health in the aged brain.
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| Gomez-Pinilla, F; Choi, J; Ryba, E A (1999) Visual input regulates the expression of basic fibroblast growth factor and its receptor. Neuroscience 88:1051-8 |
