Biomedical Research Foundation of the Academy of Athens (BRFAA), Clinical Research Centre, Laboratory of Endocrinology and Metabolism, 4 Soranou Efesiou Street, Athens, Greece.
Hippocampus. 2011 Jan;21(1):108-19. doi: 10.1002/hipo.20727.
Brain laterality has been observed in animals and humans structurally, functionally, and behaviorally. MRI and CT scans have revealed pathological and normal brain asymmetry. A coarse assessment of rat or human brain fails to expose profound left/right differences, while a finer examination of its structure reveals an array of asymmetric features. This lateralization may be derived from evolutionary, genetic, developmental, epigenetic, and pathologic factors. However, brain structure and function is complex and macroscopic or microscopic asymmetries may be hard to discern from random fluctuations. This study concentrated on the hippocampus and we explored lateralization employing a molecular high-throughput approach. Using proteomic analysis based on a combined approach of 2-D PAGE and MS, we examined differential protein expression in the hippocampi (left vs. right) of young adult male rats. Initial proteomic analysis demonstrated quantitative differences of approximately eighty proteins between the right (RH) and left hippocampus (LH). These were primarily energy-, cell metabolism-, stress-inducible chaperone proteins and cytoskeleton- proteins. Analysis revealed higher abundance of metabolic enzymes related to cellular energy metabolism, in the RH than the LH. In contrast, higher concentrations of proteins which are located mainly in astrocytes were shown in the LH than the RH. Immunoblotting of brain-specific proteins, on single animal hippocampal lysates confirmed the expression of Dynamin-1, DRP2, synapsin-1 and others, to be higher in the RH than LH lysates. These findings demonstrate major laterality in the expression of protein molecules between the two hippocampi providing a fertile field for mapping studies relating molecular, neuroimaging and functional data. Undoubtedly, asymmetries found at the animal level are hard to extrapolate to humans; however, studies in animal models will increase our understanding of the developing and adult brain and the healthy and diseased brain.
大脑的偏侧性在动物和人类中无论是在结构上、功能上还是行为上都有观察到。磁共振成像（MRI）和计算机断层扫描（CT）显示了病理性和正常的大脑不对称。对大鼠或人类大脑的粗略评估未能揭示深刻的左右差异，而对其结构的更精细检查则揭示了一系列不对称的特征。这种偏侧性可能来自于进化、遗传、发育、表观遗传和病理因素。然而，大脑的结构和功能是复杂的，宏观或微观的不对称可能难以从随机波动中辨别。本研究集中在海马体上，我们使用分子高通量方法探索了偏侧性。我们使用基于二维电泳（2-DE）和 MS 相结合的蛋白质组学分析，研究了年轻成年雄性大鼠海马体（左与右）的差异蛋白表达。初步蛋白质组学分析表明，右（RH）和左海马体（LH）之间存在约 80 种蛋白的定量差异。这些主要是能量、细胞代谢、应激诱导伴侣蛋白和细胞骨架蛋白。分析显示，RH 中与细胞能量代谢相关的代谢酶的丰度高于 LH。相反，在 LH 中显示出比 RH 更高浓度的主要位于星形胶质细胞中的蛋白。对单个动物海马体裂解物的脑特异性蛋白的免疫印迹证实，Dynamin-1、DRP2、synapsin-1 等蛋白在 RH 裂解物中的表达高于 LH 裂解物。这些发现表明，两个海马体之间的蛋白分子表达存在主要的偏侧性，为映射研究提供了一个有利的领域，将分子、神经影像学和功能数据联系起来。毫无疑问，在动物水平上发现的不对称性很难推断到人类；然而，在动物模型中的研究将增加我们对发育中和成年大脑以及健康和患病大脑的理解。
