Lossi Laura, Tamagno Ilaria, Merighi Adalberto
Department of Veterinary Morphophysiology, Rita Levi-Montalcini Center for Brain Repair, Via Leonardo da Vinci 44, 10095 Grugliasco, Italy.
J Mol Histol. 2004 Aug;35(6):621-9. doi: 10.1007/s10735-004-2189-3.
We have used the mammalian post-natal cerebellar cortex as a model to dissect out the molecular morphology of neuronal apoptosis in a well-defined population of central neurons: the cerebellar granule cells. By immunocytochemistry, in situ labeling of apoptotic cells, and analysis of cerebellar slices following particle-mediated gene transfer (biolistics), we have studied the relationship of cell death and cleavage of caspase 3, a key molecule in the execution of apoptosis, and monitored caspase 3 activation in living cells. Our results demonstrate the existence of caspase dependent and independent apoptotic pathways affecting the cerebellar granule cells at different stages of their life. Apoptosis of proliferating precursors and young pre-migratory cells occurs in the absence of caspase 3 cleavage, whereas cell death of post-mitotic post-migratory neurons is directly linked to caspase 3 activation. Data obtained from cerebellar cortex can be generalized to outline a more comprehensive picture of the cellular and molecular mechanisms of neuronal death not only in development, but also in a number of pathological conditions leading to neuronal loss.
我们已将哺乳动物出生后的小脑皮质作为模型，以剖析一群明确的中枢神经元——小脑颗粒细胞中神经元凋亡的分子形态。通过免疫细胞化学、凋亡细胞的原位标记以及粒子介导的基因转移（生物弹道学）后对小脑切片的分析，我们研究了细胞死亡与凋亡执行过程中的关键分子——半胱天冬酶3裂解之间的关系，并监测了活细胞中半胱天冬酶3的激活情况。我们的结果表明，存在影响小脑颗粒细胞生命不同阶段的半胱天冬酶依赖性和非依赖性凋亡途径。增殖前体细胞和迁移前幼细胞的凋亡在没有半胱天冬酶3裂解的情况下发生，而有丝分裂后迁移后神经元的细胞死亡则与半胱天冬酶3的激活直接相关。从小脑皮质获得的数据可以推广，以勾勒出不仅在发育过程中，而且在导致神经元丢失的许多病理状况下神经元死亡的细胞和分子机制的更全面图景。
