Departament de Bioquimica i Biologia Molecular, Institut de Neurociències, Facultat de Medicina, Torre M2, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
J Alzheimers Dis. 2009;18(4):849-65. doi: 10.3233/JAD-2009-1188.
At present it is widely accepted that there are at least two neurogenic sites in the adult mammalian brain: the subventricular zone (SVZ) of lateral ventricles and the subgranular zone (SGZ) of the hippocampus dentate gyrus. The adult proliferation rate declines with aging and is altered in several neurodegenerative pathologies including Alzheimer's disease. The aim of this work was to study whether a natural diet rich in polyphenols and polyunsaturated fatty acids (LMN diet) can modulate neurogenesis in adult mice and give insight into putative mechanisms. Results with BrdU and PCNA demonstrated that the LMN fed mice had more newly generated cells in the SVZ and SGZ, and those with DCX (undifferentiated neurons) and tyrosine hydroxylase, calretinin, and calbindin (differentiated neurons) immunostainings and western blots demonstrated a significant effect on neuronal populations, strongly supporting a positive role of the LMN diet on adult neurogenesis. In primary rat neuron cultures, the LMN cream dramatically protected against damage caused by both hydrogen peroxide and Abeta(1-42), demonstrating a potent antioxidant effect that could play a major role in the normal adult neurogenesis and, moreover, the LMN diet could have a significant effect combating the cognitive function decline during both aging and neurodegenerative diseases such as Alzheimer's disease.
目前,人们普遍认为成年哺乳动物大脑中至少有两个神经发生部位:侧脑室的室下区(SVZ)和海马齿状回的颗粒下区(SGZ)。成年后的增殖率随年龄的增长而下降,并在包括阿尔茨海默病在内的几种神经退行性疾病中发生改变。本研究旨在探讨富含多酚和多不饱和脂肪酸的天然饮食(LMN 饮食)是否能调节成年小鼠的神经发生,并深入了解潜在的机制。BrdU 和 PCNA 的结果表明,LMN 喂养的小鼠在 SVZ 和 SGZ 中有更多的新生成细胞,而 DCX(未分化神经元)和酪氨酸羟化酶、钙视网膜蛋白和钙结合蛋白(分化神经元)免疫染色和 western blot 显示对神经元群体有显著影响,强烈支持 LMN 饮食对成年神经发生的积极作用。在原代大鼠神经元培养物中,LMN 乳膏显著防止了由过氧化氢和 Abeta(1-42)引起的损伤,表现出强大的抗氧化作用,这可能在正常成年神经发生中发挥重要作用,此外,LMN 饮食可能对衰老和阿尔茨海默病等神经退行性疾病期间的认知功能下降有显著影响。