Morrison M E, Mason C A
Departments of Pathology, and Anatomy and Cell Biology, Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Neurosci. 1998 May 15;18(10):3563-73. doi: 10.1523/JNEUROSCI.18-10-03563.1998.
Granule neurons, presynaptic afferents of Purkinje cells, are potent regulators of Purkinje cell development. Purified Purkinje cells survive and differentiate poorly, whereas coculture with granule neurons enhances their survival and dendritic development. Here we investigate the role of neurotrophins in granule-Purkinje cell interactions. BDNF or NT-4 improves, but NT-3 or CNTF reduces, survival of isolated Purkinje cells. When granule neurons are present, however, BDNF or NT-4 treatment leads to Purkinje cell loss. This decrease is overcome by anti-BDNF or TrkB-IgG-blocking reagents or by CNQX, a non-NMDA glutamate receptor antagonist. Furthermore, BDNF increases the spine density on the surviving Purkinje cells. These results suggest that Purkinje cell survival and differentiation are context-dependent and require a balance between neurotrophin- and activity-dependent signaling.
颗粒神经元是浦肯野细胞的突触前传入神经元,是浦肯野细胞发育的有效调节因子。纯化的浦肯野细胞存活和分化较差,而与颗粒神经元共培养可提高其存活率和树突发育。在这里,我们研究神经营养因子在颗粒-浦肯野细胞相互作用中的作用。BDNF或NT-4可改善分离的浦肯野细胞的存活,但NT-3或CNTF会降低其存活率。然而,当存在颗粒神经元时,BDNF或NT-4处理会导致浦肯野细胞丢失。抗BDNF或TrkB-IgG阻断试剂或非NMDA谷氨酸受体拮抗剂CNQX可克服这种减少。此外,BDNF增加了存活的浦肯野细胞上的棘密度。这些结果表明,浦肯野细胞的存活和分化取决于环境,需要神经营养因子和活性依赖信号之间的平衡。