Reductions in size and total DNA of cerebrum and cerebellum in adult mice after corticosterone treatment in infancy

Abstract

This study was designed to examine the long-term effects on the brain of intensive corticosterone treatment during the period of rapid postnatal brain growth and maturation. Mice were given a single subcutaneous implantation of a pellet of corticosterone at 2 days of age. This produced a temporary interference with growth that resulted in a 10% reduction in body weight of the adults; a slightly greater reduction in cerebral weights and a 21% reduction in cerebellar weights. Determinations of DNA, RNA and cholesterol were made, as indices of cell number and maturation. the total DNA of the normal mouse cerebrum increased 25% between 2 and 14 days of age, while cerebellar DNA increased 580%. Total cerebral DNA did not change in control mice between 14 and 350 days of age. Corticosterone given between 2 and 14 days reduced total cerebral DNA 18% at 14 days and 10% at 8 months; and reduced cerebellar DNA 25%. In the cerebrum there was a small but significant decrease in cholesterol at all ages studied. There was a transient decrease in the RNA DNA ratio. The findings indicate that corticosterone given in infancy interfered with the synthesis of DNA, RNA, and protein in the brain, and produced an irreversible reduction in brain size and cell numbers, which was particularly marked in the cerebellum, because of the high rate of postnatal mitosis characteristic of certain cerebellar neurons.