Mooney S M, Miller M W
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA 52242-1000, USA.
Brain Res Dev Brain Res. 2000 Oct 28;123(2):103-17. doi: 10.1016/s0165-3806(00)00081-x.
Naturally occurring neuronal death (NOND) is generally considered to be apoptotic. Apoptosis is an active form of cell death in which the regulation of specific proteins produces anti- or pro-apoptotic signals. Two of the protein families involved in this regulation are the bcl proteins and caspases. A quantitative immunoblotting technique was used to examine the temporal expression of bcl-2, bax, and two isoforms of caspase 3 (an active 20 kDa isoform and the inactive 32 kDa precursor) throughout the developing neuraxis. Long-Evans rat fetuses were collected on gestational day (G) 16 and G19, and pups were harvested on postnatal day (P) 0, P3, P6, P12, P21, and P30. Brains were divided into five segments: cortex, thalamus, midbrain, medulla/pons, and cerebellum. In general, the expression of bax increased and the ratio of bcl-2 expression to bax expression decreased concurrent with published data on the onset of NOND in a given area. The timing of these events was paralleled by an increase in the expression of active caspase 3. Unlike the bcl proteins, caspase 3 expression returned toward fetal levels as the brain matured. The timing of the changes in bcl protein and caspase expression show that both protein families are involved in promoting neuronal death. Reductions in caspase expression (and not bcl-2 and bax expression) are key to ending the period of NOND.
自然发生的神经元死亡（NOND）通常被认为是凋亡性的。凋亡是一种细胞死亡的主动形式，其中特定蛋白质的调节产生抗凋亡或促凋亡信号。参与这种调节的两个蛋白质家族是bcl蛋白和半胱天冬酶。采用定量免疫印迹技术检测整个发育中的神经轴中bcl-2、bax和半胱天冬酶3的两种同工型（活性20 kDa同工型和无活性32 kDa前体）的时间表达。在妊娠第16天（G16）和第19天（G19）收集Long-Evans大鼠胎儿，并在出生后第0天（P0）、第3天（P3）、第6天（P6）、第12天（P12）、第21天（P21）和第30天（P30）收获幼崽。大脑分为五个部分：皮层、丘脑、中脑、延髓/脑桥和小脑。一般来说，bax的表达增加，bcl-2表达与bax表达的比值降低，这与给定区域NOND开始的已发表数据一致。这些事件的时间与活性半胱天冬酶3表达的增加平行。与bcl蛋白不同，随着大脑成熟，半胱天冬酶3的表达恢复到胎儿水平。bcl蛋白和半胱天冬酶表达的变化时间表明这两个蛋白质家族都参与促进神经元死亡。半胱天冬酶表达的降低（而不是bcl-2和bax的表达）是结束NOND时期的关键。
