Saroglitazar 通过上调 Wnt/β Catenin 信号增强大鼠痴呆模型的记忆功能和成神经元形成

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-09-12 DOI:10.1021/acschemneuro.4c00167

Sandeep Kumar Mishra, Vaibhav Mishra

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引用次数: 0

摘要

过氧化物酶体增殖激活受体（PPARs）已成为治疗各种神经退行性疾病的有希望的靶点。研究表明，PPAR α和amp; γ都能单独调节神经炎症和胰岛素抵抗等各种病理生理事件，而众所周知，神经炎症和胰岛素抵抗会对神经发生产生不同程度的影响。我们的研究旨在评估沙格列扎尔（SGZR）（一种双重 PPAR 激动剂）对脑室内链脲佐菌素（ICV STZ）诱导的大鼠痴呆症中成年神经发生和空间学习记忆的影响。我们发现，与 ICV STZ 处理的大鼠相比，每次口服 4 毫克/千克剂量的 SGZR 能显著改善大鼠的学习和记忆能力。室管膜下区（SVZ）和齿状回（DG）的神经发生显著增加，表现为5-溴-2′-脱氧尿苷（BrdU）+细胞、BrdU+ nestin+细胞和双皮质素（DCX）+细胞数量的增加。使用 SGZR 还能降低糖原合酶激酶 3β （GSK3β）的活性形式，从而增强 β-catenin 的核转位。Wnt 转录因子和靶基因表达的增强表明，Wnt 信号的上调可能与所观察到的神经发生的增加有关。因此，可以得出结论，SGZR可通过上调Wnt β-catenin信号增强ICV STZ处理大鼠的记忆功能和成体神经发生。

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Saroglitazar Enhances Memory Functions and Adult Neurogenesis via Up-Regulation of Wnt/β Catenin Signaling in the Rat Model of Dementia

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Saroglitazar Enhances Memory Functions and Adult Neurogenesis via Up-Regulation of Wnt/β Catenin Signaling in the Rat Model of Dementia

Peroxisome proliferator-activated receptors (PPARs) have emerged as a promising target for the treatment of various neurodegenerative disorders. Studies have shown that both PPAR α & γ individually modulate various pathophysiological events like neuroinflammation and insulin resistance, which are known to variedly affect neurogenesis. Our study aimed to evaluate the effect of saroglitazar (SGZR), a dual PPAR agonist, on adult neurogenesis and spatial learning and memory, in intracerebroventricular streptozotocin (ICV STZ)-induced dementia in rats. We have found that SGZR at the dose of 4 mg/kg per oral showed significant improvement in learning and memory compared to ICV STZ-treated rats. A substantial increase in neurogenesis was observed in the subventricular zone (SVZ) and the dentate gyrus (DG), as indicated by an increase in the number of 5-bromo-2′-deoxyuridine (BrdU)⁺ cells, BrdU⁺ nestin⁺ cells, and doublecortin (DCX)⁺cells. Treatment with SGZR also decreased the active form of glycogen synthase kinase 3β (GSK3β) and hence enhanced the nuclear translocation of the β-catenin. Enhanced expression of Wnt transcription factors and target genes indicates that the up-regulation of Wnt signaling might be involved in the observed increase in neurogenesis. Hence, it can be concluded that the SGZR enhances memory functions and adult neurogenesis via the upregulation of Wnt β-catenin signaling in ICV STZ-treated rats.

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来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.