Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan; Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan; Omics Center, Center of Medical Innovation and Translational Research, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan; United Graduate School of Child Development, Osaka University, Suita 565-0871, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Suita 565-0871, Japan; Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka 541-8567, Japan.
Behav Brain Res. 2024 Jun 25;468:115040. doi: 10.1016/j.bbr.2024.115040. Epub 2024 May 7.
Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases.
神经毒素已被广泛研究，特别是在神经科学领域。它们会导致神经元产生毒性损伤、氧化应激和炎症，从而引发神经元功能障碍和神经退行性疾病。在这里，我们展示了一种基于硅的产氢剂（Si 基剂）在由 6-羟多巴胺（6-OHDA）诱导的幼年神经毒性小鼠模型中的神经保护作用。Si 基剂在肠道中产生氢气，同时具有抗氧化和抗炎作用。然而，Si 基剂对病变以外的神经变性以及由此引起的行为改变的影响在很大程度上尚未可知。此外，先前的研究并未探讨 Si 基剂在哺乳期和婴儿期使用时对神经退行性变的保护作用。在这项研究中，我们使用小鼠模型展示了 Si 基剂在哺乳期和婴儿期对 6-OHDA 的神经保护作用。Si 基剂可防止多巴胺能神经元的退化和死亡以及纹状体（STR）和腹侧被盖区（VTA）中多巴胺能纤维的丢失，这是由 6-OHDA 引起的。此外，Si 基剂对内侧前额叶皮质（mPFC）L2/3 神经元轴突起始段（AIS）的长度也具有神经保护作用。结果，Si 基剂减轻了由 6-OHDA 诱导的幼年神经毒性小鼠模型中的多动行为。这些结果表明，Si 基剂是一种有效的神经保护剂和抗氧化剂，可对抗大脑中的神经毒性作用，为 Si 基剂作为神经系统疾病的神经保护剂提供了可能性。
