BDNF accelerates gene expression in cultured cerebellar granule neurons

Abstract

This study reports that in purified cultures of postnatal cerebellar granule cells, BDNF significantly accelerated GABA A receptor α6 subunit (GABA A α6) mRNA expression, a marker for terminally differentiated cerebellar granule neurons, and also accelerated p21 cip1 expression. p21 cip1 is a general cyclin-dependent kinase (Cdk) inhibitor that can inhibit progression through the cell cycle. Alternatively, the expression of p27 kip1, another Cdk inhibitor closely related to p21 cip1, is not modified by BDNF. In cultured granule cells, the increase in p21 cip1 expression induced by BDNF occurred after dividing granule cells had left the cell cycle and thus was not required to direct granule neuron precursors out of the cell cycle. p21 cip1 may have an alternative function during granule neuron terminal differentiation, separate from its ability to regulate cell cycle exit. This report shows that, in vitro, BDNF accelerates granule cell gene expression and may thus modulate cerebellar granule cell differentiation.