Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232-0414, USA.
Brain Res. 2011 Jun 29;1398:1-12. doi: 10.1016/j.brainres.2011.04.046. Epub 2011 May 5.
Selenoprotein P (Sepp1) is an important protein involved in selenium (Se) transport and homeostasis. Severe neurologic dysfunction develops in Sepp1 null mice (Sepp1(-/-)) fed a selenium-deficient diet. Sepp1(-/-) mice fed a selenium-deficient diet have extensive degeneration of the brainstem and thalamus, and even when supplemented with selenium exhibit subtle learning deficits and altered basal synaptic transmission and short-term plasticity in the CA1 region of the hippocampus. The goal of this study was to delineate the regional progression of neurodegeneration in the brain, determine the extent of neuronal cell death, and evaluate neurite structural changes within the hippocampus of Sepp1(-/-) mice. Whole brain serial sections of wild-type and Sepp1(-/-) mice maintained on selenium-deficient or supplemented diets over the course of 12 days from weaning were evaluated with amino cupric silver neurodegeneration stain. The neurodegeneration was present in all regions upon weaning and progressed over 12 days in Sepp1(-/-) mice fed selenium-deficient diet, except in the medial forebrain bundle and somatosensory cortex where the neurodegeneration developed post-weaning. The neurodegeneration was predominantly axonal, however the somatosensory cortex and lateral striatum showed silver-stained neurons. Morphologic analysis of the hippocampus revealed decreased dendritic length and spine density, suggesting that loss of Sepp1 also causes subtle changes in the brain that can contribute to functional deficits. These data illustrate that deletion of Sepp1, and presumably selenium deficiency in the brain, produce both neuronal and axonal degeneration as well as more moderate and potentially reversible neurite changes in the developing brain.
硒蛋白 P（Sepp1）是一种重要的蛋白质，参与硒（Se）的运输和稳态。在喂食缺乏硒的饮食的 Sepp1 缺失小鼠（Sepp1（-/-））中，会出现严重的神经功能障碍。喂食缺乏硒的饮食的 Sepp1（-/-）小鼠，其脑干和丘脑广泛退化，即使补充硒，也会出现轻微的学习缺陷，并改变海马 CA1 区的基础突触传递和短期可塑性。本研究的目的是描绘大脑中神经退行性变的区域进展，确定神经元死亡的程度，并评估 Sepp1（-/-）小鼠海马中的神经突结构变化。用氨基酸铜银神经退行性变染色法评估在断奶后 12 天内，持续喂食缺乏硒或补充硒的饮食的野生型和 Sepp1（-/-）小鼠的全脑连续切片。在断奶时，所有区域都存在神经退行性变，并且在喂食缺乏硒的 Sepp1（-/-）小鼠中，在 12 天内进展，除了在中脑束和体感皮层，这些区域的神经退行性变是在断奶后发生的。神经退行性变主要是轴突性的，但体感皮层和外侧纹状体显示出银染神经元。海马的形态学分析显示树突长度和棘密度减少，表明 Sepp1 的缺失也会导致大脑中出现细微变化，从而导致功能缺陷。这些数据表明，Sepp1 的缺失，以及大脑中可能的硒缺乏，会导致神经元和轴突的退行性变，以及发育中的大脑中更温和且可能可逆的神经突变化。
