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 fluid rich in lipids and inflammatory 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 fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid. Methods An animal model was established by injecting human ACP cyst fluid 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 profile for analysis. Data verification was performed through pathological means. Results ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression 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 fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74–APP is significantly strengthened between inflammatory 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 fluid. Conclusion In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory 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 fluid damage to the hypothalamus and neurodegenerative diseases.

Effects of Craniotomy and Endoscopic Endonasal Transsphenoidal Surgery on Bodyweight in Adult-Onset Craniopharyngioma: A Single-Center Retrospective Study

“…The damage to the VMH or arcuate nucleus predominantly contributes to extreme energy imbalance and progressive weight gain [ 33 ]. In addition to physical impairment, a study also found that adamantinomatous craniopharyngioma oily fluid may cause obesity by triggering inflammatory activation of microglia and damage to hypothalamus neurons [ 34 ]. Therefore, minimizing the damage to the hypothalamus caused by surgery is crucial for stable postoperative weight.…”

The Challenging Management of Craniopharyngiomas in Adults: Time for a Reappraisal?

“…This senescent phenotype could be the cause (or the consequence) of shortened telomeres that have been observed in ACPs harboring mutations as compared to their counterparts that do not harbor mutations [ 50 ]. A recent study showed that, in addition to the mass effect exerted by the tumor, the hypothalamic sequelae of ACPs could also result from a direct and detrimental effect of inflammatory factors contained in the tumor cyst [ 51 ]. As such, by injecting human ACP cyst fluid into the bilateral hypothalamus of mice, growth retardation and increased obesity occurred together with a decreased expression of genes involved in growth regulation and energy metabolism in hypothalamic neurons.…”

“…As such, by injecting human ACP cyst fluid into the bilateral hypothalamus of mice, growth retardation and increased obesity occurred together with a decreased expression of genes involved in growth regulation and energy metabolism in hypothalamic neurons. Eventually, β-amyloid deposition, a marker of neurodegenerative diseases, was also observed in the hypothalamic area of injected mice [ 51 ]. The immune system appears to also play a role in the pathogenesis of ACPs, as evidenced by the release of immunosuppressive factors, such as IL-10, in the ACP cyst fluid [ 48 ].…”

Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification

“…Craniopharyngioma (CP) is a benign slow growing (WHO grade 1) sellar/suprasellar neoplasm that arises from the epithelial remnants in the anterior part of Rathke pouch at the infundibular stalk juncture with pituitary gland [ 45 ]. According to the 2021 WHO classification, CPs include two distinct entities, adamantinomatous CP (ACP) and papillary CP (PCP), formerly considered only subtypes, given that now is known that they exhibit different clinical and molecular features [ 46 ], and will be therefore discussed separately.…”