School for Mental Health & Neuroscience, Maastricht University, Maastricht, The Netherlands.
Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
Hippocampus. 2019 Feb;29(2):102-110. doi: 10.1002/hipo.23015. Epub 2018 Dec 6.
Dystrophin is an important protein within the central nervous system. The absence of dystrophin, characterizing Duchenne muscular dystrophy (DMD), is associated with brain related comorbidities such as neurodevelopmental (e.g., cognitive and behavioural) deficits and epilepsy. Especially mutations in the downstream part of the DMD gene affecting the dystrophin isoforms Dp140 and Dp71 are found to be associated with cognitive deficits. However, the function of Dp140 is currently not well understood and its expression pattern has previously been implicated to be developmentally regulated. Therefore, we evaluated Dp140 and Dp71 expression in human hippocampi in relation to cognitive functioning in patients with drug-resistant temporal lobe epilepsy (TLE) and post-mortem controls. Hippocampal samples obtained as part of epilepsy surgery were quantitatively analyzed by Western blot and correlations with neuropsychological test results (i.e., memory and intelligence) were examined. First, we demonstrated that the expression of Dp140 does not appear to differ across different ages throughout adulthood. Second, we identified an inverse correlation between memory loss (i.e., verbal and visual memory), but not intelligence (i.e., neither verbal nor performance), and hippocampal Dp140 expression. Finally, patients with TLE appeared to have similar Dp140 expression levels compared to post-mortem controls without neurological disease. Dp140 may thus have a function in normal cognitive (i.e., episodic memory) processes.
肌营养不良蛋白是中枢神经系统中的一种重要蛋白质。缺乏肌营养不良蛋白，即杜氏肌营养不良症（DMD）的特征，与与大脑相关的合并症有关，如神经发育（例如认知和行为）缺陷和癫痫。特别是影响肌营养不良蛋白异构体 Dp140 和 Dp71 的 DMD 基因下游部分的突变与认知缺陷有关。然而，目前对 Dp140 的功能还了解甚少，其表达模式以前被认为与发育有关。因此，我们评估了与耐药性颞叶癫痫（TLE）患者和死后对照认知功能相关的人类海马中 Dp140 和 Dp71 的表达。通过 Western blot 对癫痫手术中获得的海马样本进行定量分析，并检查与神经心理学测试结果（即记忆和智力）的相关性。首先，我们证明 Dp140 的表达在整个成年期的不同年龄段似乎没有差异。其次，我们发现记忆丧失（即言语和视觉记忆）与海马 Dp140 表达呈负相关，但与智力（即言语和表现均无关）无关。最后，与无神经疾病的死后对照相比，TLE 患者的 Dp140 表达水平似乎相似。因此，Dp140 可能在正常认知（即情景记忆）过程中具有功能。
