Department of Pharmacology, Yale University, 333 Cedar St, New Haven, CT, USA.
Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA.
Sci Rep. 2021 Jan 27;11(1):2372. doi: 10.1038/s41598-021-81650-5.
Neuronal calcium sensor 1 (NCS1) regulates a wide range of cellular functions throughout the mammalian nervous systems. Altered NCS1 expression is associated with neurodevelopmental and neurodegenerative diseases. Previous studies focused on affective and cognitive behaviors in NCS1 knockout (KO) mice, but little is known about the physiological and pathological states associated with the loss of NCS1 in the peripheral nervous system. We previously reported that NCS1 expression was reduced following paclitaxel-induced peripheral neuropathy. Here, we comprehensively investigated the phenotypes of NCS1-KO mice through a battery of behavioral tests examining both central and peripheral nervous systems. Generally, only mild differences were observed in thermal sensation and memory acquisition between NCS1-WT and -KO male mice, but not in female mice. No differences were observed in motor performance, affective behaviors, and hearing in both sexes. These results suggest that NCS1 plays a modulatory role in sensory perceptions and cognition, particularly in male mice. NCS1 has been proposed as a pharmacological target for various diseases. Therefore, the sex-specific effects of NCS1 loss may be of clinical interest. As we examined a constitutive KO model, future studies focusing on various conditional KO models will further elucidate the precise physiological significance of NCS1.
神经元钙传感器 1（NCS1）在哺乳动物神经系统中调节广泛的细胞功能。NCS1 表达的改变与神经发育和神经退行性疾病有关。先前的研究集中在 NCS1 敲除（KO）小鼠的情感和认知行为上，但对于外周神经系统中 NCS1 缺失与生理和病理状态相关的了解甚少。我们之前报道过紫杉醇诱导的周围神经病变后 NCS1 表达减少。在这里，我们通过一系列行为测试全面研究了 NCS1-KO 小鼠的表型，这些测试检查了中枢和外周神经系统。一般来说，在雄性小鼠中，NCS1-WT 和-KO 之间在热感觉和记忆获取方面仅观察到轻微差异，但在雌性小鼠中则没有。在两性的运动表现、情感行为和听力方面均未观察到差异。这些结果表明，NCS1 在感觉感知和认知中发挥调节作用，特别是在雄性小鼠中。NCS1 已被提议作为各种疾病的药理学靶点。因此，NCS1 缺失的性别特异性效应可能具有临床意义。由于我们检查了一个组成型 KO 模型，未来聚焦于各种条件性 KO 模型的研究将进一步阐明 NCS1 的精确生理意义。
