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Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

ABSTRACT: Introduction: The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fuid rich in lipids and infammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors. Objective: The objective of this study was to construct a reliable animal model of ACP cyst fuid-induced hypotha lamic injury and explore the specifc mechanism of hypothalamic injury caused by cyst fuid. Methods: An animal model was established by injecting human ACP cyst fuid into the bilateral hypothalamus of mice. ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profle for analysis. Data verifcation was performed through pathological means. Results: ACP cystic fuid caused growth retardation and an increased obesity index in mice, afected the expres sion of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp–Mc3r. ACP cystic fuid signifcantly caused infammatory activation of hypothalamic microglia. The cellular interaction of CD74–APP is signifcantly strengthened between infammatory activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fuid. Conclusion: In this study, a novel animal model of ACP cystic fuid-hypothalamic injury was established. For the frst time, it was found that ACP cystic fuid can trigger infammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74–APP interaction and deposition of β-amyloid, implying that there may be a similar mechanism between ACP cystic fuid damage to the hypothalamus and neurodegenerative diseases.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE206861 | GEO | 2022/06/25

REPOSITORIES: GEO

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Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

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