Agasse Fabienne, Roger Michel, Coronas Valérie
CNRS: UMR 6187, Laboratoire de Biomembranes et Signalisation Cellulaire, Faculté des Sciences, Université de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France.
Eur J Neurosci. 2004 Mar;19(6):1459-68. doi: 10.1111/j.1460-9568.2004.03259.x.
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.
摘要 在成年哺乳动物大脑中，室下区（SVZ）维持着神经发生活动。非神经源性区域的损伤可刺激SVZ细胞增殖，并促使受影响区域产生新的神经元。因此，我们研究了特定微环境线索对SVZ神经发生活动可能产生的调控作用。为此，将新生SVZ神经球置于来自成年神经源性SVZ或非神经源性大脑皮层的可扩散信号存在的环境中，其中非神经源性大脑皮层要么预先用已知的凋亡诱导剂星形孢菌素处理过（凋亡皮层），要么未处理过（未处理皮层）。为了将相互作用限制在可溶性信号范围内，将外植体通过微孔膜与SVZ神经球隔开。结果表明，SVZ自身释放的分子通过增加增殖和减少凋亡来促进SVZ细胞群体的扩增。相反，未处理皮层的因子通过降低增殖来减少SVZ细胞群体的扩增。此外，SVZ或未处理皮层的因子分别促进或抑制神经元分化。在发生凋亡性损伤后，皮层因子不再起抑制作用，而是通过增加增殖来促进SVZ细胞群体的扩增。使用用不同外植体条件培养的培养基后，对细胞数量的这些影响得以重现，但热灭活后这些影响不再存在，这表明蛋白质参与其中。这些发现表明，神经源性SVZ传递促进神经发生的自分泌/旁分泌信号，而非神经源性大脑皮层释放抑制增殖和神经元分化的信号。有趣的是，在凋亡性损伤后，大脑皮层这种组成性的生长抑制作用发生了反转。
