Instituto de Neurociencias, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Autónoma de Barcelona, Bellaterra, Barcelona, Spain.
Behav Brain Res. 2012 Mar 17;228(2):261-71. doi: 10.1016/j.bbr.2011.11.014. Epub 2011 Nov 22.
We examined whether LMN diet, reported to induce neurogenesis in adult mice, was able to antagonize the age-related behavioural impairment and neuropathology in wild type (WT) mice and Tg2576 mice, a mouse model of Alzheimer's disease (AD). Thirteen-month-old mice (once the amyloid (Aβ) plaques were formed) were fed with the LMN diet for 5 months, and in the last 2 months of the regimen they received a battery of behavioural tests. In general, both aging and (to a higher extent) Tg2576 genotype deteriorated sensorimotor reflexes, exploratory behaviour in the hole board, activity (but not anxiety) in the elevated plus-maze, ambulation in the home cage during the dark phase, and spatial learning in the Morris water maze. LMN diet did not affect the detrimental effects observed in sensorimotor reflexes, but clearly reversed the effects of both aging and Tg2576 genotype. This behavioural amelioration was correlated with a 70% increase in cellular proliferation in subventricular zone (SVZ) of the brain, but did not correlate with a decrease of amyloid plaques. In contrast, administration of LMN diet to 10 months old mice (before the plaques are formed) strongly suggested a putative delay in the formation of plaques, as indicated by a decreasing tendency of soluble and fibrillar Aβ levels in hippocampus which correlated with a decrease in Aβ (1-40, 1-42) plasma content. Herein we describe for the first time that LMN diet rich in polyphenols, dry fruits and cocoa, was able to decrease behavioural deterioration caused by aging and Tg2576 genotype and to delay the Aβ plaque formation. These results corroborate the increasing importance of polyphenols as human dietary supplements in amelioration of the cognitive impairment during aging and neurological disorders such as AD.
我们研究了 LMN 饮食（据报道可在成年小鼠中诱导神经发生）是否能够拮抗野生型（WT）小鼠和阿尔茨海默病（AD）小鼠模型 Tg2576 小鼠的年龄相关行为损伤和神经病理学。13 月龄的小鼠（一旦形成淀粉样蛋白（Aβ）斑块）用 LMN 饮食喂养 5 个月，在饮食方案的最后 2 个月接受一系列行为测试。总的来说，衰老和（更大程度上）Tg2576 基因型都恶化了感觉运动反射、洞板中的探索行为、高架十字迷宫中的活动（但不包括焦虑）、暗期在家笼中的活动以及 Morris 水迷宫中的空间学习。LMN 饮食并未影响到观察到的感觉运动反射的有害影响，但明显逆转了衰老和 Tg2576 基因型的影响。这种行为改善与大脑侧脑室下区（SVZ）的细胞增殖增加 70%相关，但与 Aβ 斑块的减少无关。相比之下，在斑块形成之前（10 个月大时）给 10 月龄的小鼠施用 LMN 饮食强烈表明斑块形成有延迟的趋势，这表现为海马中可溶性和纤维状 Aβ 水平呈下降趋势，这与 Aβ（1-40、1-42）血浆含量减少相关。在此，我们首次描述了富含多酚、干果和可可的 LMN 饮食能够降低衰老和 Tg2576 基因型引起的行为恶化，并延迟 Aβ 斑块形成。这些结果证实了多酚作为人类膳食补充剂在改善衰老和神经退行性疾病（如 AD）期间认知障碍方面的重要性日益增加。
