The Effects of Neonatal Hydrocortisone on Rat Cerebellar Development

Abstract

The development of the cerebellar cortex was studied in rats treated neonatally (days 1–4) with hydrocortisone. Effects on the external granular layer (EGL) and development of the cerebellar laminæ in lobule VIII were determined by quantitative light-microscopic methods. The ''birthdays'' and numbers of various interneurons generated from the EGL were determined autoradiographically in rats injected with ³H-thymidine on days 1,2,5,7,10,15,21 or 24, and sacrificed on day 72. The growth of the EGL and the mitotic index were reduced during the hydrocortisone treatment, but rebounded following termination of the treatment. Nevertheless, the total number of cells produced by the EGL did not recover to control values and the disappearance of the EGL was not prolonged. In treated rats sacrificed at 72 days, the cerebellar foliation pattern in sagittal sections of vermis was reproducibly changed. In lobule VIII, the total area and areas of the molecular layer and internal granular layer were decreased by 14, 17 and 12%, respectively. The total numbers of all postnatally formed interneurons were decreased by this hormonal treatment, but the number of stellate cells in the outer molecular layer was most affected. During the treatment, greater proportions of both granule cells and interneurons in the inner molecular layer (mainly basket cells) completed early final cell divisions. However, ''birthdays'' for the majority of granule cells were delayed probably as a result of increased cell proliferation in the EGL following release from the HCA treatment. Stellate cell birthdays were unaffected. The developmental consequences following this hormonal manipulation are discussed with respect to possible glucocorticoid actions. The implications of these results for normal rat cerebellar development are also considered.