The Ginkgo biloba extract modulates the balance between proliferation and differentiation in the olfactory epithelium of adult mice following bulbectomy.

Abstract - The adult olfactory receptor neurons (ORNs), located in the olfactory epithelium (OE) are permanently renewed thanks to neuronal progenitors present in the deep part of the OE, the globose basal cells (GBCs). Following the ablation of their synaptic target, the olfactory bulb (OB), ORNs degenerate by apoptosis and a wave of neurogenesis, including proliferation of GBCs and neuronal differentiation of their progeny, restores the olfactory function. The Ginkgo biloba extract (EGb 761) (Beaufour Ipsen, France) was administered to adult mice at the doses of 50 or 100 mg/kg, following bilateral bulbectomy and its effects on the expression of PCNA, reflecting the number of proliferating GBCs and on growth associated protein 43 (GAP-43), expressed by differentiating neurons were measured by Western blotting. PCNA expression peaked 9 days post-bulbectomy in untreated animals, but 7 days post-lesion in EGb 761-treated animals. A simultaneous reduction in GAP-43 expression suggested that EGb 761 may temporarily favor the proliferation of GBCs rather than their entry into the differentiation pathway. Probably as a consequence of the earlier onset of the neurogenetic response to bulbectomy, neuronal differentiation was enhanced in the OE, 3 weeks post-bulbectomy. These data suggest that EGb 761 may have beneficial effects upon neurogenesis in the OE through changing the balance between proliferation and differentiation.