Department of Sciences, University of Roma Tre, Rome, Italy.
J Cell Physiol. 2013 Jul;228(7):1561-7. doi: 10.1002/jcp.24315.
Although a great knowledge about the patho-physiological roles of cholesterol metabolism perturbation in several organs has been reached, scarce information is available on the regulation of cholesterol homeostasis in the brain where this lipid is involved in the maintenance of several of neuronal processes. Currently, no study is available in literature dealing how and if sex and age may modulate the major proteins involved in the regulatory network of cholesterol levels in different brain regions. Here, we investigated the behavior of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) and low-density lipoprotein receptor (LDLr) in adult (3-month-old) and aged (12-month-old) male and female rats. The analyses were performed in four different brain regions: cortex, brain stem, hippocampus, and cerebellum which represent brain areas characterized by different neuronal cell types, metabolism, cytoarchitecture and white matter composition. The results show that in hippocampus HMGR is lower (30%) in adult female rats than in age-matched males. Differences in LDLr expression are also observable in old females with respect to age-matched males: the protein levels increase (40%) in hippocampus and decrease (20%) in cortex, displaying different mechanisms of regulation. The mechanism underlying the observed modifications are ascribable to Insig-1 and SREBP-1 modulation. The obtained data demonstrate that age- and sex-related differences in cholesterol homeostasis maintenance exist among brain regions, such as the hippocampus and the prefrontal cortex, important for learning, memory and affection. Some of these differences could be at the root of marked gender disparities observed in clinical disease incidence, manifestation, and prognosis.
尽管人们对胆固醇代谢紊乱在多个器官中的病理生理作用有了深入的了解，但关于胆固醇在大脑中的动态平衡调节的信息却很少，因为胆固醇在维持多种神经元过程中起着重要作用。目前，文献中尚无研究探讨性别和年龄如何以及是否可以调节不同脑区胆固醇水平调节网络中的主要蛋白。在这里，我们研究了成年（3 个月大）和老年（12 个月大）雄性和雌性大鼠不同脑区中 3-羟-3-甲基戊二酰辅酶 A 还原酶（HMGR）和低密度脂蛋白受体（LDLr）的行为。分析在四个不同的脑区进行：大脑皮层、脑干、海马体和小脑，它们分别代表具有不同神经元细胞类型、代谢、细胞结构和白质组成的脑区。结果表明，成年雌性大鼠海马体中的 HMGR 比同龄雄性大鼠低（30%）。老年雌性大鼠的 LDLr 表达也存在差异：与同龄雄性相比，其蛋白水平在海马体中增加（40%），而在皮层中减少（20%），表现出不同的调节机制。观察到的这些变化的机制归因于 Insig-1 和 SREBP-1 的调节。所得数据表明，胆固醇动态平衡维持存在于大脑不同区域之间的年龄和性别差异，例如海马体和前额叶皮层，这些区域对于学习、记忆和情感非常重要。其中一些差异可能是临床疾病发病率、表现和预后方面明显的性别差异的根源。
