Juan Chen, Zhigao Xiang, Zhuo Zhang, Yan Yang, Kai Shu, Ting Lei
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Western blotting, immunohistochemistry, and immunofluorescence techniques were employed to examine changes in the hippocampal tau protein, Aβ, and associated signaling pathways.</p><p><strong>Results: </strong>The tumor cells secreting growth hormone increased the secretion of growth hormone, resulting in changes in body size and endocrine functions, thus causing acromegaly. The acromegaly model showed deficiencies in working memory and spatial memory. Hyperphosphorylation of tau protein was observed in the hippocampus of the acromegaly model, but no Aβ deposition was observed. The acromegaly model exhibits hippocampal growth hormone (GH) resistance, decreased expression of GH receptors, and subsequently reduced expression activity of the PI3K-Akt-GSK3β signaling pathway, which is responsible for the hyperphosphorylation of tau protein.</p><p><strong>Conclusion: </strong>The prolonged elevation of GH and insulin-like growth factor 1 caused by acromegaly may lead to abnormalities in the SD rat's PI3K-Akt-GSK3β signaling pathway, subsequently resulting in hyperphosphorylation of the hippocampal tau protein and cognitive impairment.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151995/pdf/","citationCount":"0","resultStr":"{\"title\":\"Acromegalic Rat Model Presented Cognitive Impairments and Tau Hyperphosphorylation in the Hippocampus.\",\"authors\":\"Juan Chen, Zhigao Xiang, Zhuo Zhang, Yan Yang, Kai Shu, Ting Lei\",\"doi\":\"10.1159/000537813\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Acromegaly patients, in addition to the most prominent physical and endocrine changes, also exhibit a higher risk of cognitive dysfunction. 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引用次数: 0
摘要
导言:肢端肥大症患者除了最突出的身体和内分泌变化外,还表现出较高的认知功能障碍风险。然而,肢端肥大症患者出现认知障碍的原因和机制仍不清楚:方法:通过皮下注射肿瘤细胞诱导肢端肥大症大鼠,持续监测体重和激素以确认肢端肥大症的发生。进行行为评估,包括开阔地测试、新物体识别测试和巴恩斯迷宫测试,以评价动物的认知功能。采用Western印迹、免疫组化和免疫荧光技术检测海马tau蛋白、Aβ和相关信号通路的变化:结果:分泌生长激素的肿瘤细胞增加了生长激素的分泌,导致体型和内分泌功能发生变化,从而引起肢端肥大症。肢端肥大症模型显示出工作记忆和空间记忆的缺陷。在肢端肥大症模型的海马中观察到 tau 蛋白过度磷酸化,但未观察到 Aβ 沉积。肢端肥大症模型表现出海马生长激素(GH)抵抗,GH受体表达减少,PI3K-Akt-GSK3β信号通路的表达活性随之降低,而PI3K-Akt-GSK3β信号通路是造成tau蛋白过度磷酸化的原因:结论:肢端肥大症引起的GH和胰岛素样生长因子1(IGF-1)水平长期升高可能导致SD大鼠PI3K-Akt-GSK3β信号通路异常,进而导致海马tau蛋白过度磷酸化和认知障碍。
Acromegalic Rat Model Presented Cognitive Impairments and Tau Hyperphosphorylation in the Hippocampus.
Introduction: Acromegaly patients, in addition to the most prominent physical and endocrine changes, also exhibit a higher risk of cognitive dysfunction. However, the reasons and mechanisms underlying cognitive impairments in acromegaly patients remain unknown.
Methods: Acromegalic rats were induced by subcutaneous injection of tumor cells, with continuous monitoring of the body weight and hormones to confirm the occurrence of acromegaly. Behavioral assessments, including open field test, novel object recognition test, and Barnes maze test, were conducted to evaluate the animals' cognitive function. Western blotting, immunohistochemistry, and immunofluorescence techniques were employed to examine changes in the hippocampal tau protein, Aβ, and associated signaling pathways.
Results: The tumor cells secreting growth hormone increased the secretion of growth hormone, resulting in changes in body size and endocrine functions, thus causing acromegaly. The acromegaly model showed deficiencies in working memory and spatial memory. Hyperphosphorylation of tau protein was observed in the hippocampus of the acromegaly model, but no Aβ deposition was observed. The acromegaly model exhibits hippocampal growth hormone (GH) resistance, decreased expression of GH receptors, and subsequently reduced expression activity of the PI3K-Akt-GSK3β signaling pathway, which is responsible for the hyperphosphorylation of tau protein.
Conclusion: The prolonged elevation of GH and insulin-like growth factor 1 caused by acromegaly may lead to abnormalities in the SD rat's PI3K-Akt-GSK3β signaling pathway, subsequently resulting in hyperphosphorylation of the hippocampal tau protein and cognitive impairment.
期刊介绍:
''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.