Lestaevel P, Airault F, Racine R, Bensoussan H, Dhieux B, Delissen O, Manens L, Aigueperse J, Voisin P, Souidi M
Laboratoire de Radiotoxicologie Expérimentale (LRTOX), Service de Radiobiologie et d'Epidémiologie (SRBE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), BP no° 17, 92262 Fontenay-aux-Roses CEDEX and BP no° 166, 26702, Pierrelatte CEDEX, France,
J Mol Neurosci. 2014 Jul;53(3):469-79. doi: 10.1007/s12031-013-0038-0. Epub 2013 Jun 9.
Alzheimer's disease is associated with genetic risk factors, of which the apolipoprotein E (ApoE) is the most prevalent, and is affected by environmental factors that include education early in life and exposure to metals. The industrial and military use of depleted uranium (DU) resulted in an increase of its deposition in some areas and led to a possible environmental factor. The present study aims to ascertain the effects on the behaviour and the metabolism of cholesterol and acetylcholine of ApoE-/- mice exposed to enriched environment (EE) and exposed to DU (20 mg/L) for 14 weeks. Here we show that ApoE-/- mice were unaffected by the EE and their learning and memory were similar to those of the non-enriched ApoE-/- mice. ApoE-/- mice showed a significant decrease in total (-16 %) and free (-16 %) cholesterol in the entorhinal cortex in comparison to control wild-type mice. Whatever the housing conditions, the exposure to DU of ApoE-/- mice impaired working memory, but had no effect on anxiety-like behaviour, in comparison to control ApoE-/- mice. The exposure of ApoE-/- mice to DU also induced a trend toward higher total cholesterol content in the cerebral cortex (+15 %) compared to control ApoE-/- mice. In conclusion, these results demonstrate that enriched environment does not ameliorate neurobehaviour in ApoE-/- mice and that ApoE mutation induced specific effects on the brain cholesterol. These findings also suggested that DU exposure could modify the pathology in this ApoE model, with no influence of housing conditions.
阿尔茨海默病与遗传风险因素相关，其中载脂蛋白E（ApoE）最为常见，且受环境因素影响，这些环境因素包括早年教育和接触金属。贫铀（DU）在工业和军事上的使用导致其在某些地区的沉积增加，并成为一种可能的环境因素。本研究旨在确定暴露于富集环境（EE）并接触14周DU（20毫克/升）对ApoE基因敲除小鼠行为以及胆固醇和乙酰胆碱代谢的影响。我们发现，ApoE基因敲除小鼠不受EE影响，其学习和记忆能力与未处于富集环境的ApoE基因敲除小鼠相似。与对照野生型小鼠相比，ApoE基因敲除小鼠内嗅皮质中的总胆固醇（-16%）和游离胆固醇（-16%）显著降低。无论饲养条件如何，与对照ApoE基因敲除小鼠相比，ApoE基因敲除小鼠接触DU会损害其工作记忆，但对焦虑样行为没有影响。与对照ApoE基因敲除小鼠相比，ApoE基因敲除小鼠接触DU还导致大脑皮质中总胆固醇含量有升高趋势（+15%）。总之，这些结果表明，富集环境并不能改善ApoE基因敲除小鼠的神经行为，且ApoE突变对脑胆固醇有特定影响。这些发现还表明，接触DU可能会改变该ApoE模型中的病理学，且不受饲养条件影响。
