Effects of developmental age, brain region and time in culture on long-term proliferation and multipotency of neural stem cell populations

Neural stem cells (NSCs) in the murine subventricular zone (SVZ) niche allow life-long neurogenesis. During the first postnatal month and throughout aging, the decrease of neuroblasts and the rise of astrocytes results in diminished neurogenesis and increased astrocyte:neuron ratio. Also, a different neurogenic activity characterizes the SVZ periventricular region (LV, lateral ventricle) as compared to its rostral extension (RE). In order to investigate whether and to what extent these physiological modifications may be ascribed to intrinsic changes of the endogenous NSC/progenitor features, we performed a functional analysis on NSCs isolated and cultured from LV and RE tissues at distinct postnatal stages that are marked by striking modifications to the SVZ niche in vivo. We evaluated the effect of age and brain region on long-term proliferation and multipotency, and characterized the cell type composition of NSC-derived progeny, comparing this make-up to that of region- and age-matched primary neural cultures. Furthermore, we analyzed the effect of prolonged in vitro expansion on NSC functional properties. We documented age- and region-dependent differences on the clonogenic efficiency and on the long-term proliferative capacity of NSCs. Also, we found age- and region-dependent quantitative changes in the cell composition of NSC progeny (decreased quantity of neurons and oligodendrocytes; increased amount of astroglial cells) and these differences were maintained in long-term cultured NSC populations. Overall, these data strengthen the hypothesis that age- and region-dependent differences in neurogenesis (observed in vivo) may be ascribed to the changes in the intrinsic developmental program of the NSC populations.