Marcos P, González-Fuentes J, Castro-Vázquez L, Lozano M V, Santander-Ortega M J, Rodríguez-Robledo V, Villaseca-González N, Arroyo-Jiménez M M
Cellular Neuroanatomy and Molecular Chemistry of Central Nervous System, Faculty of Pharmacy and Faculty of Medicine, University of Castilla-La Mancha, CRIB (Centro Regional de Investigaciones Biomédicas), Albacete, Spain.
J Anat. 2018 Apr;232(4):699-715. doi: 10.1111/joa.12769. Epub 2018 Jan 8.
Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann's glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.
其高代谢率和高多不饱和脂肪酸含量使大脑对氧化损伤非常敏感。在大脑中,神经元代谢速率极高,会产生大量活性氧和自由基,这些物质在神经元内积累,导致细胞内稳态和完整性改变,最终造成不可逆损伤和细胞死亡。氧化还原代谢失衡及随后的神经退行性变在正常衰老过程中不断加剧,导致学习、记忆以及运动功能出现一些与年龄相关的变化。抗氧化剂的神经保护功能对于维持良好的脑内稳态和充足的神经元功能至关重要。维生素E和维生素C是两种重要的抗氧化剂,它们分别通过特定载体αTTP和SVCT2被脑细胞摄取。本研究的目的是利用免疫组织化学方法,在一个脑衰老迹象较少且对氧化损伤具有较高抵抗力的小鼠模型中,确定这些维生素转运体在脑内的分布模式。两种载体在整个大脑中广泛分布,在4个月、12个月、18个月和24个月大的小鼠中,其分布模式保持相似。一般来说,αTTP和SVCT2位于相同区域,但它们似乎具有互补的分布模式。仅在下丘、内嗅皮层、背侧海马下托和几个皮质区域检测到双标记细胞体。此外,使用针对NeuN的双重免疫组织化学分析了神经元中αTTP和SVCT2的存在情况,结果显示αTTP存在于伯格曼胶质细胞中,而SVCT2不存在。这些转运体在与学习、记忆和运动控制相关的脑区中的存在提供了一个解剖学基础,这可能解释了该动物模型对脑氧化应激具有较高抵抗力的原因,而这与老年时更好的运动表现和学习能力相关。