DEVELOPMENTAL AND AGING CHANGES IN PROTEIN CONCENTRATION AND 2',3'-CYCLIC NUCLEOSIDEMONOPHOSPHATE PHOSPHODIESTERASE ACTIVITY (EC 3.1.4.16) IN HUMAN CEREBRAL WHITE AND GRAY MATTER AND SPINAL CORD

Abstract— The concentration of protein as assayed by the Lowry method and the specific activity of 2′.3’-cyclic nucleosidemonophosphate phosphodiesterase (CNP), an enzyme characteristic of the myelin sheath, were determined in human CNS tissues obtained at autopsy from subjects ranging in age from 26 weeks gestation to 83 y. CNP activity in cerebral white matter samples was very low until approx 2 months of age when it increased rapidly, reaching near-adult levels by 2 y of age. CNP activity in adult (15–60 y) cerebral white matter was 8.1 ± 1.0 μmol/min/mg protein (mean ±s.d. ). The protein concentration of cerebral white matter increased from 64 mg/g wet tissue at 26 weeks gestation to adult levels (118.5 ± 10.0 mg/g wet tissue) by 16–18 months. CNP activity in cerebral gray matter was initially very low and showed only a small increase during development to adult values of approx 1.4 μmol/min/mg protein. In spinal cord, adult values (3.7 ± 0.56 μmol/min/mg protein) were found shortly after birth. The increase in CNP activity to near-adult values occurred earlier in cross-sections of cervical spinal cord than in cerebral white matter. The increase in spinal cord protein concentration showed a similar trend (adult values = 103.1 ± 9.5 mg/g wet tissue). The white matter protein concentration decreased significantly with age over the 15–83 y interval examined but the CNP specific activity in white matter did not. The protein concentration of the 61–83 y group was 8% lower than that of the 15–60 y group. The spinal cord protein concentration decreased significantly and the spinal cord CNP specific acitivity increased significantly with increasing time between death and sample freezing. The sex of the individual had no significant effect on any of the variables examined. The developmental curves obtained for these tissues are consistent with the hypothesis that CNP is an intrinsic myelin component in human CNS myelin. The marked increase in CNP activity in white matter coincides with the period of rapid myelin deposition as determined by other parameters. CNP activity may be useful as an index of myelination in human CNS tissues.