Fabienne Agasse | PubMed Health

PubMed2006

Endogenous factors derived from embryonic cortex regulate proliferation and neuronal differentiation of postnatal subventricular zone cell cultures.

In rodents, the subventricular zone (SVZ) harbours neural stem cells that proliferate and produce neurons throughout life. Previous studies showed that factors released by the developing cortex promote neurogenesis in the embryonic ventricular zone. In the present report, we studied in the rat the possible involvement of endogenous factors derived from the embryonic cortex in the regulation of the development of postnatal SVZ cells. To this end, SVZ neurospheres were maintained with explants or conditioned media (CM) prepared from embryonic day (E) 13, E16 or early postnatal cortex. We demonstrate that early postnatal cortex-derived factors have no significant effect on SVZ cell proliferation or differentiation. In contrast, E13 and E16 cortex release diffusible, heat-labile factors that promote SVZ cell expansion through increased proliferation and reduced cell death. In addition, E16 cortex-derived factors stimulate neuronal differentiation in both early postnatal and adult SVZ cultures. Fibroblast growth factor (FGF)-2- but not epidermal growth factor (EGF)-immunodepletion drastically reduces the mitogenic effect of E16 cortex CM, hence suggesting a major role of endogenous FGF-2 released by E16 cortex in the stimulation of SVZ cell proliferation. The evidence we provide here for the regulation of SVZ cell proliferation and neuronal differentiation by endogenous factors released from embryonic cortex may be of major importance for brain repair research.

Age Factors↗

PubMed2004

Neurogenic and intact or apoptotic non-neurogenic areas of adult brain release diffusible molecules that differentially modulate the development of subventricular zone cell cultures.

Abstract In the adult mammalian brain, neurogenic activity is maintained in the subventricular zone (SVZ). Damage to non-neurogenic areas can stimulate SVZ cell proliferation and trigger addition of new neurons in the affected areas. We therefore examined the possible control exerted by specific microenvironment cues on SVZ neurogenic activity. To this end, neonatal SVZ neurospheres were maintained in the presence of diffusible signals derived from the adult neurogenic SVZ or from the non-neurogenic cerebral cortex either previously treated (apoptotic cortex) or not (untreated cortex) with staurosporine, a known apoptosis inducer. To restrict interactions to soluble signals, the explants were separated from the SVZ neurospheres by a microporous membrane. The results indicated that molecules released by the SVZ itself promoted the expansion of SVZ cell population through increased proliferation and reduced apoptosis. In contrast, untreated cortex factors reduced the expansion of SVZ cell population by decreasing proliferation. In addition, SVZ or untreated cortex factors, respectively, promoted or inhibited neuronal differentiation. Following apoptotic damage, cortex factors no longer inhibited and instead promoted the expansion of the SVZ cell population by increasing proliferation. These effects on cell numbers were replicated following use of culture media conditioned with the different explants but were no longer present following heat inactivation, which indicates that proteins were involved. These findings indicate that the neurogenic SVZ delivers autocrine/paracrine signals that promote neurogenesis whereas the non-neurogenic cerebral cortex releases signals that inhibit proliferation and neuronal differentiation. Interestingly, this constitutive growth inhibitory effect of the cerebral cortex is inverted following apoptotic lesion.

Animals↗