School of Psychology, Cardiff University, 70 Park Place, Cardiff, Wales, CF10 3AT, UK.
Neuroscience. 2011 Feb 3;174:71-83. doi: 10.1016/j.neuroscience.2010.11.025. Epub 2010 Nov 18.
A mouse model of amyloid pathology was used to first examine using a cross sectional design changes in retrosplenial cortex activity in transgenic mice aged 5, 11, 17, and 23 months. Attention focused on: (1) overt amyloid labeled with β-amyloid((1-42)) and Congo Red staining, (2) metabolic function assessed by the enzyme, cytochrome oxidase, and (3) neuronal activity as assessed indirectly by the immediate-early gene (IEG), c-Fos. Changes in cytochrome oxidase and c-Fos activity were observed in the retrosplenial cortex in Tg2576 mice as early as 5 months of age, long before evidence of plaque formation. Subsequent analyses concentrating on this early dysfunction revealed at 5 months pervasive, amyloid precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex and selective afferents (anterior thalamus, hippocampus), which was associated with the observed c-Fos hyporeactivity. These findings indicate that retrosplenial cortex dysfunction occurs during early stages of amyloid production in Tg2576 mice and may contribute to cognitive dysfunction.
我们首先使用淀粉样蛋白病理学的小鼠模型，通过横断面设计，在 5、11、17 和 23 月龄的转基因小鼠中，研究了后扣带回皮层活动的变化。我们重点关注以下几个方面：（1）β-淀粉样蛋白（1-42）和刚果红染色的明显淀粉样蛋白；（2）细胞色素氧化酶评估的代谢功能；（3）通过即刻早期基因（IEG）c-Fos 间接评估的神经元活性。早在斑块形成之前，Tg2576 小鼠的后扣带回皮层就已经观察到细胞色素氧化酶和 c-Fos 活性的变化，这种变化早在 5 个月大时就出现了。随后的集中分析表明，在 5 个月时，后扣带回皮层普遍存在淀粉样前体蛋白（APP）衍生肽的积累，以及选择性传入（前丘脑、海马），这与观察到的 c-Fos 反应性降低有关。这些发现表明，Tg2576 小鼠的后扣带回皮层功能障碍发生在淀粉样蛋白产生的早期阶段，可能导致认知功能障碍。
