A single peripheral injection of basic fibroblast growth factor (bFGF) stimulates granule cell production and increases cerebellar growth in newborn rats

The control of neuronal number is critical for coordinating innervation and target organ requirements. Although basic fibroblast growth factor (bFGF) is known to regulate neuron number in the developing embryonic cortex, its potential role during postnatal brain development remains undefined. To add ress this issue, the cerebellum, a site of postnatal neurogenesis, was used . Previously, we found that a single peripheral injection of bFGF in newbor n rats elicited mitosis of neuronal precursors in the external germinal lay er (EGL)8 h after administration. We now define the sustained effects of bF GF treatment on postnatal granule cell production and cerebellar growth. Se venty-two h after a single injection of bFGF (20 ng/g) in newborn rats, the fraction of BrdU-labeled cells in the EGL increased by 46% without alterin g apoptotic cell number, consistent with enhanced precursor proliferation, Moreover, bFGF increased mitotically labeled cells by 100% and total cell d ensity by 33% in the internal granular layer (IGL), the final destination o f the EGL precursors, Because cerebellar volume also increased by 22%, bFGF -induced proliferation enhanced generation of total IGL neurons and increas ed cerebellar growth. These morphometric measures were corroborated indepen dently by using DNA quantitation: cerebellar DNA content increased 16% afte r bFGF injection, consistent with increased neuron number, Furthermore, usi ng DNA quantitation as an index, increased total cerebellar cell number eli cited by bFGF injection persisted beyond the neurogenetic period, until P35 , We conclude that a single postnatal injection of bFGF increases granule n euron number and enhances cerebellar growth following mitotic stimulation. (C) 2001 John Wiley & Sons. Inc.