Objective

Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and oxidative damage induced by acrolein is hypothesized to involve in the etiology of Alzheimer’s disease (AD). Calorie restriction (CR) is the only non-genetic intervention that has consistently been verified to retard aging by ameliorating oxidative stress. Therefore, we investigated the effects of CR on acrolein-induced neurotoxicity in Sprague-Dawley (SD) rats.

Methods

A total of 45 weaned and specific-pathogen-free SD rats (male, weighing 180–220 g) were gavage-fed with acrolein (2.5 mg/kg/day) and fed ab libitum of 10 g/day or 7 g/day (representing 30% CR regimen), or gavage-fed with same volume of tap water and fed al libitum as vehicle control for 12 weeks. After behavioral test conducted by Morris Water Maze, SD rats were sacrificed and brain tissues were prepared for histochemical evaluation and Western blotting to detect alterations in oxidative stress, BDNF/TrkB pathway and key enzymes involved in amyloid precursor protein (APP) metabolism.

Results

Treatment with 30% CR in SD rats significantly attenuated acrolein-induced cognitive impairment. Oxidative damage including deletion of glutathione and superoxide dismutase and sharp rise in malondialdehyde were notably improved by 30% CR. Further study suggested that 30% CR showed protective effects against acrolein by modulating BDNF/TrkB signaling pathways. Moreover, 30% CR restored acrolein-induced changes of APP, β-secretase, α-secretase and receptor for advanced glycation end products.

Conclusion

These findings suggest that CR may provide a promising approach for the treatment of AD, targeting acrolein.

中文翻译：

---

热量限制改善丙烯醛诱导的大鼠神经毒性

客观的

丙烯醛是一种高度反应性的不饱和醛，是一种普遍存在的环境污染物，据推测由丙烯醛引起的氧化损伤与阿尔茨海默氏病（AD）的病因有关。热量限制（CR）是唯一经证实已通过缓解氧化应激来延缓衰老的非遗传干预措施。因此，我们研究了CR对Sprague-Dawley（SD）大鼠中丙烯醛诱导的神经毒性的影响。

方法

总共对45只断奶和无特定病原体的SD大鼠（雄性，体重180-220 g）用丙烯醛（2.5 mg / kg /天）管饲，并随意喂食10 g /天或7 g /天（代表30％的CR方案），或以相同体积的自来水管饲，并作为媒介物对照随意饲喂12周。经过Morris Water Maze进行的行为测试后，处死SD大鼠，准备脑组织进行组织化学评估和Western blotting，以检测氧化应激，BDNF / TrkB途径和淀粉样前体蛋白（APP）代谢涉及的关键酶的变化。

结果

SD大鼠中30％CR的治疗显着减轻了丙烯醛诱导的认知障碍。谷胱甘肽和超氧化物歧化酶的缺失以及丙二醛含量的急剧上升等氧化损伤可通过30％CR显着改善。进一步的研究表明30％的CR通过调节BDNF / TrkB信号通路显示出对丙烯醛的保护作用。此外，有30％的CR恢复了丙烯醛诱导的APP，β-分泌酶，α-分泌酶和晚期糖基化终产物受体的变化。

结论

这些发现表明，CR可能为针对丙烯醛的AD提供有前途的治疗方法。