Alleviation of cognitive deficits via upregulation of chondroitin sulfate biosynthesis by lignan sesamin in a mouse model of neuroinflammation.
Alleviation of cognitive deficits via upregulation of chondroitin sulfate biosynthesis by lignan sesamin in a mouse model of neuroinflammation.
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DOI：
10.1016/j.jnutbio.2022.109093
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发表时间：
2022-06
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通讯作者：
J. Yamada;Shoichiro Maeda;Mariko Soya;Hidefumi Nishida;K. Iinuma;S. Jinno
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作者：
J. Yamada;Shoichiro Maeda;Mariko Soya;Hidefumi Nishida;K. Iinuma;S. Jinno
木脂素是植物衍生的化合物，作为部分雌激素激动剂。硫酸软骨素蛋白聚糖（CSPG）代表细胞外基质的主要组分之一。在这里，我们的目的是了解芝麻素（SES），一种主要的木脂素化合物，在小鼠海马中的CSPGs的生物合成和降解的作用，因为CSPGs通过促进成年神经发生在认知功能的调节中起着关键作用。在脂多糖（LPS）处理的小鼠（神经炎症诱导的认知缺陷模型）的海马中，SES给药降低了促炎细胞因子白细胞介素-1 β的表达。与LPS处理的小鼠海马中CSPGs的生物合成和降解相关的基因的表达通过SES给药增加和减少。此外，在LPS处理的小鼠的海马中，通过紫藤凝集素（WFA）的CSPGs的弥漫性细胞外基质标记通过SES给药增加。神经干细胞的密度，迟发性放大细胞，和新生颗粒细胞在LPS处理的小鼠海马也增加SES管理。此外，SES诱导的基因表达，WFA标记，和成年的LPS治疗小鼠的神经发生的变化更明显的背侧海马（认知中心）比腹侧海马（情绪中心）。LPS和SES给药均不影响运动活动、焦虑样行为和抑郁相关行为。然而，在LPS处理的小鼠的上下文记忆和感觉运动门控的损害恢复SES管理。我们的研究结果表明，SES可以通过上调CSPGs促进成年海马神经发生，这可能会减轻神经炎症引起的认知障碍。
Lignans are plant-derived compounds that act as partial estrogen agonists. Chondroitin sulfate proteoglycans (CSPGs) represent one of the major components of the extracellular matrix. Here we aimed to understand the role of sesamin (SES), a major lignan compound, in the biosynthesis and degradation of CSPGs in the mouse hippocampus because CSPGs play a key role in the regulation of cognitive functions through the promotion of adult neurogenesis. The expression of the pro-inflammatory cytokine interleukin-1β was decreased by SES administration in the hippocampus of lipopolysaccharide (LPS)-treated mice, a model of neuroinflammation-induced cognitive deficits. The expression of genes related to biosynthesis and degradation of CSPGs in the hippocampus of LPS-treated mice was both increased and decreased by SES administration. Further, the diffuse extracellular matrix labeling of CSPGs byWisteriafloribundaagglutinin (WFA) in the hippocampus of LPS-treated mice was increased by SES administration. The densities of neural stem cells, late transit-amplifying cells, and newborn-granule cells in the hippocampus of LPS-treated mice were also increased by SES administration. Moreover, SES-induced alterations in gene expression, WFA labeling, and adult neurogenesis in LPS-treated mice were more evident in the dorsal hippocampus (center of cognition) than in the ventral hippocampus (center of emotion). Neither LPS nor SES administration affected locomotor activity, anxiety-like behavior, and depression-related behavior. However, impairments in contextual memory and sensorimotor gating in LPS-treated mice were recovered by SES administration. Our results show that SES can promote adult hippocampal neurogenesis through the upregulation of CSPGs, which may alleviate cognitive deficits induced by neuroinflammation.