First, the age-related impairment in the astrocytic support
of neurite outgrowth was reversed by down-regulating
GFAP with RNAi. Second, age-like impairments of astrocytic
support of neurite growth were induced by transfecting
young adult astrocytes with GFAP cDNA. While a general
relationship between GFAP in reactive gliosis and neuronal
sprouting is widely recognized during lesion response, our
studies show that increased GFAP expression during aging is
an independent factor in impaired neurite outgrowth in the absence
of lesions and of astrocytes with reactive morphology.
This point is emphasized, because the negative associations
of neurite growth with GFAP expression have been observed
after experimental lesions, which induce large reactive astrocytes
not found in the unlesioned cultures. These findings
raise the possibility that increased GFAP during aging is not
only secondary to neurodegeneration and allows the hypothesis
that the spontaneous age-related increase of GFAP is a
factor in impaired synaptic plasticity during aging.