Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.
Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.
复制标题
DOI：
10.3389/fnins.2016.00089
复制
发表时间：
2016
影响因子：
4.3
通讯作者：
Suárez J
中科院分区：
文献类型：
--
作者：
Pérez-Martín M;Rivera P;Blanco E;Lorefice C;Decara J;Pavón FJ;Serrano A;Rodríguez de Fonseca F;Suárez J
过氧化物酶体增殖物激活受体α（过氧化物酶体增殖物激活受体α）配体已被证明可以通过增强神经发生来调节脑损伤（如缺血和辐射）后的恢复。本研究探讨了PPARα受体基因缺失对成年人脑神经前体细胞（NPC）增殖率的影响。这项研究是在老年Pparα−/−小鼠中进行的，这些小鼠暴露于营养（治疗）和环境（游戏）富集20天。我们对成年大脑主要神经发生区（齿状回颗粒下区（SGZ）、侧脑室脑室下区（SVZ）和/或下丘脑）中含有复制细胞DNA标记物5-溴-2 ′-脱氧尿苷（BrdU+）和未成熟神经元标记物双皮质素（Dcx+）的细胞进行了免疫组织化学分析。结果表明，在老化过程中（2，6，和18个月），在分析的神经源性区域中的BrdU+细胞的数量减少，以及在SGZ中的Dcx+细胞。Pparα缺乏减轻了18月龄小鼠SVZ中NPC增殖（BrdU+细胞）的年龄相关性减少。虽然在衰老过程中在SGZ中未检测到基因型对NPC增殖的影响，但在6个月大的Pparα−/−小鼠的SGZ中观察到Dcx+细胞数量的明显减少。将18个月大的小鼠暴露于营养和环境富集物中，逆转了Pparα−/−诱导的NPC增殖损伤。富集环境没有改变18个月大Pparα−/−小鼠中SGZ Dcx+细胞的数量。这些结果确定了PPARα受体作为一个潜在的靶点，以抵消自然观察到的与衰老和贫困环境相关的成人NPC增殖下降。
Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα−/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα−/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα−/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα−/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.