Alteration of the activity and molecular from of thymidine kinase during development and aging in the mouse cerebellum

Abstract

Protein, DNA and thymidine kinase levels were assayed during development and aging in the mouse cerebellum. A roughly parallel increase in protein and DNA content occurred from birth, reaching a plateau at 18 days; these adult levels increased by 30% in the 23 month-old cerebellum. Thymidine kinase activity reached a maximum at 6 postnatal days, then decreased steadily to reach, at 18 days, the low level that was maintained in the adult. The thymidine kinase synthesized in the aged cerebellum differed from that in the neonate by having (i) an increased specific activity, (ii) a faster migrating species upon electrophoresis, (iii) an inhibition by dCTP, and (iv) a lower affinity for the substrate thymidine (higher Km). Mathematical calculations indicated the appearance of a larger number of smaller sized cells in the aged cerebellum, when compared with the young adult. Histological analysis established that the newly synthesized cells were localized in the molecular layer of the old cerebellum. It appears that senescence in the mouse cerebellum may be associated with an increased synthesis of glial cells.