Silva Rui, Lu Jie, Wu Yan, Martins Luis, Almeida Osborne F X, Sousa Nuno
Neuroscience Group, Life and Health Sciences Research Institute, ICVS, University of Minho, 4710-057 Braga, Portugal.
Exp Neurol. 2006 Aug;200(2):321-31. doi: 10.1016/j.expneurol.2006.02.119. Epub 2006 Apr 19.
Neurogenesis and apoptosis occur contemporaneously in the postnatal hippocampal dentate gyrus and have been implicated in mood and cognitive disorders. Particularly, neurogenesis correlates with the manifestation of antidepressant effects, but its quantitative and topographical relationship with concomitant cell death has not been investigated. Accordingly, we applied stereological measurements to obtain synchronized topographical maps of these two events in rats aged 1 and 3 months under basal conditions; the two ages were chosen to represent neuro-developmental windows during which cell proliferation and death are occurring at peak and relatively steady levels, respectively. Our analysis shows that apoptotic cells are evenly distributed throughout the dentate gyrus, although the incidence of apoptosis decreased gradient-wise from the tip of the suprapyramidal layer and was highest in the external third of the granule cell layer. Interestingly, apoptosis was higher in the left hippocampus. In addition, we confirm previous less stringent studies demonstrating that neurogenesis occurs differentially in the dorsal-ventral axis of the hippocampus and in suprapyramidal-infrapyramidal blades of the dentate gyrus. These results raise intriguing new questions regarding the coordinated regulation of hippocampal neurogenesis and apoptosis since the two processes apparently share common regulatory factors. In addition, these findings open questions with respect to the functional significance of topographical gradients in neurogenesis and apoptosis in the context of the etiopathogenesis of neuropsychiatric diseases and the reported dependence on the efficacy of therapeutic agents on the generation of new hippocampal neurons.
神经发生和细胞凋亡在出生后海马齿状回中同时发生，并与情绪和认知障碍有关。特别是，神经发生与抗抑郁作用的表现相关，但其与伴随的细胞死亡的定量和地形关系尚未得到研究。因此，我们应用体视学测量方法，在基础条件下获得1个月和3个月龄大鼠这两个事件的同步地形图；选择这两个年龄代表神经发育窗口，在此期间细胞增殖和死亡分别处于峰值和相对稳定水平。我们的分析表明，凋亡细胞在整个齿状回中均匀分布，尽管凋亡发生率从锥体上层尖端呈梯度下降，且在颗粒细胞层外三分之一处最高。有趣的是，左侧海马体中的凋亡更高。此外，我们证实了先前不太严格的研究结果，即神经发生在海马体的背腹轴以及齿状回的锥体上-锥体下叶片中存在差异。由于这两个过程显然共享共同的调节因子，这些结果引发了关于海马体神经发生和细胞凋亡协调调节的有趣新问题。此外，这些发现就神经精神疾病病因学背景下神经发生和细胞凋亡中地形梯度的功能意义以及所报道的治疗药物疗效对新海马神经元生成的依赖性提出了问题。
