Aging-dependent changes in the cellular composition of the mouse brain and spinal cord

Abstract

Although the impact of aging on the function of the central nervous system is known, only a limited amount of information is available about accompanying changes affecting the cellular composition of the brain and spinal cord. In the present work we used the isotropic fractionator method to reveal aging-associated changes in the numbers of neuronal and non-neuronal cells harbored by the brain and spinal cord. The experiments were performed on 15-week, 7-month, 13-month, and 25-month-old female mice. The major parts of the brain were studied separately, including the isocortex, hippocampus, cerebellum, olfactory bulb, and the remaining part (i.e., 'rest of brain'). The proliferative capacity of each structure was assessed by counting the number of Ki-67-positive cells. We found no aging-dependent change when the cellular composition of the isocortex was studied. In contrast, the neuronal and non-neuronal cell numbers of the hippocampus decreased in the 7-25-month period. The neuronal cell number of the olfactory bulb showed positive age-dependence between 15. weeks and 13. months of age and presented a significant decrease thereafter. The cerebellum was characterized by an age-dependent decrease of its neuronal cell number and density. In the rest of brain, the non-neuronal cell number increased with age. The neuronal and non-neuronal cell numbers of the spinal cord increased, whereas its neuronal and non-neuronal densities decreased with age. The number of proliferating cells showed a marked age-dependent decrease in the hippocampus, olfactory bulb, and rest of the brain. In contrast, the number of Ki-67-positive cells increased with age in both the cerebellum and spinal cord. In conclusion, aging-dependent changes affecting the cellular composition of the mouse central nervous system are present but they are diverse and region-specific.