Cerebellar cortical neurogenesis following exposure to lipopolysaccharide in ferret neonates.

INTRODUCTION: Granular neurons arise from external granular precursors (EGPs) in the external granule layer and internal granular progenitors (IGPs) in the internal granule layer (IGL) during cerebellar cortical histogenesis in ferrets. Additionally, IGPs have a potency on differentiating into Bergmann glia and astrocytes. This study aimed to clarify the effects of lipopolysaccharide (LPS) on granular neurogenesis in the developing ferret cerebellum and its association with the proliferation, differentiation, and apoptosis of EGPs and IGPs. METHODS: LPS (500 µg/g body weight) was administered to ferrets at postnatal days (PDs) 6 and 7. Ferrets also received 5-ethynyl-2'-deoxyuridine (EdU) and 5-bromo-2'-deoxyuridine (BrdU) on PDs 5 and 7, respectively, to label post-proliferative and proliferating cells at the time of LPS exposure. RESULTS: Two h after BrdU injection (PD 7), the densities of proliferating BrdU- and post-proliferative EdU-labeled cells did not differ in the external granular layer, molecular/Purkinje cell layers (ML/PCL), or IGL between LPS-exposed and control ferrets. BrdU-labeled cells contained 55-83% cells immunostained for proliferating cell nuclear antigen (PCNA), selectively expressed in IGPs. The S100-immunostained ratio among BrdU-labeled cells was significantly higher in the ML/PCL, but lower in the IGL of LPS-exposed ferrets compared to controls. On PD 20, NeuN-positive granular neurons generated on PD 7 (BrdU-labeled) were significantly denser in the IGL of LPS-exposed ferrets. CONCLUSION: These findings suggest that LPS enhances granular neurogenesis in the developing cerebellum of ferret neonates. LPS may have a location-specific effect on the glial differentiation of proliferating IGPs: enhancing and reducing in the ML/PCL and IGL, respectively.