Wellcome Centre for Integrative Neuroimaging, Nuffield Dept of Clinical Neurosciences, Oxford, United Kingdom.
Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
PLoS One. 2023 Feb 2;18(2):e0281264. doi: 10.1371/journal.pone.0281264. eCollection 2023.
The atypical protein tyrosine phosphatase enzyme, dual-specificity phosphate 15 (DUSP15) is thought to be activated by myelin regulatory factor (MyRF) and to have a role in oligodendrocyte differentiation. Here, we assess whether Dusp15 is reduced in the hippocampus of mice with conditional knock-out of Myrf in oligodendrocyte precursor cells. Using quantitative polymerase chain reaction (qPCR) we found that Dusp15 expression was indeed lower in these mice. Alterations in myelin have been associated with Alzheimer's disease (AD), autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Symptoms of these disorders can include impairments of object recognition and attention. We, therefore tested the mice in the object recognition task (ORT) and 5-choice serial reaction time task (5CSRTT). However, we did not find behavioural impairments indicating that attentional abilities and object recognition are not impacted by reduced oligodendrogenesis and hippocampal Dusp15 expression. Gaining insight into the role of newly formed oligodendrocytes and Dusp15 expression is helpful for the development of well targeted treatments for myelin dysregulation.
非典型蛋白酪氨酸磷酸酶酶，双特异性磷酸酶 15（DUSP15）被认为被髓鞘调节因子（MyRF）激活，并在少突胶质细胞分化中发挥作用。在这里，我们评估了条件敲除少突胶质细胞前体细胞中 Myrf 的小鼠的海马体中 Dusp15 是否减少。使用定量聚合酶链反应（qPCR），我们发现这些小鼠中的 Dusp15 表达确实较低。髓鞘的改变与阿尔茨海默病（AD）、自闭症谱系障碍（ASD）和注意缺陷/多动障碍（ADHD）有关。这些疾病的症状包括物体识别和注意力受损。因此，我们在物体识别任务（ORT）和 5 选择序列反应时间任务（5CSRTT）中测试了这些小鼠。然而，我们没有发现行为障碍表明注意力能力和物体识别不受少突胶质形成和海马体 Dusp15 表达减少的影响。深入了解新形成的少突胶质细胞和 Dusp15 表达的作用有助于开发针对髓鞘失调的靶向治疗方法。
