Hannan Chaudhry Talha, Jeremiah Munguti Kilonzo, Idenya Pamela Mandela
Department of Human Anatomy and Medical Physiology, University of Nairobi, Nairobi, Kenya.
Anat Cell Biol. 2025 Mar 31;58(1):76-85. doi: 10.5115/acb.24.088. Epub 2024 Oct 31.
Aromatase inhibitors are increasingly being used as adjuvant therapy for hormone-responsive cancers. These drugs may reduce the endogenous estrogen production in the cerebellum. Prolonged use has been associated with symptoms such as ataxia, poorer balance performance and diminished verbal memory, suggesting impaired cerebellar function. Thus, this study sought to outline the structural basis for the cerebellar deficits observed. Twenty-seven male rats (3 baseline, 15 experimental, 9 control) aged three months were recruited with the intervention group receiving 0.5 mg/kg of letrozole daily for 50 days by oral gavage while the control group received normal saline. Their cerebella were harvested for histological processing on days 20, 35, and 50. Photomicrographs were taken and analysed using Fiji ImageJ software. The dendritic spine densities and Purkinje linear densities were coded and analyzed using IBM SPSS Statistics version 25.0. A -value of ≤0.05 was considered significant. A temporal decline in the Purkinje linear density as well as pyknosis and cytoplasmic eosinophilia was noted in the intervention group (=0.165). Further, the dendritic spine density of the Purkinje neurons in the intervention group was markedly reduced (=0.01). The reduction in the linear cell density and the dendritic spine density of the Purkinje cells following letrozole administration may provide an anatomical basis for the functional cerebellar deficits seen in chronic aromatase inhibitor use.
芳香化酶抑制剂越来越多地被用作激素反应性癌症的辅助治疗药物。这些药物可能会减少小脑内源性雌激素的产生。长期使用与共济失调、平衡能力下降和言语记忆减退等症状有关,提示小脑功能受损。因此,本研究旨在概述所观察到的小脑缺陷的结构基础。招募了27只3个月大的雄性大鼠(3只为基线组,15只为实验组,9只为对照组),干预组通过口服灌胃每天给予0.5mg/kg来曲唑,持续50天,而对照组给予生理盐水。在第20、35和50天采集它们的小脑进行组织学处理。拍摄显微照片并使用斐济ImageJ软件进行分析。使用IBM SPSS Statistics 25.0版本对树突棘密度和浦肯野细胞线性密度进行编码和分析。P值≤0.05被认为具有统计学意义。干预组观察到浦肯野细胞线性密度随时间下降以及核固缩和细胞质嗜酸性变(P = 0.165)。此外,干预组浦肯野神经元的树突棘密度明显降低(P = 0.01)。来曲唑给药后浦肯野细胞的线性细胞密度和树突棘密度降低可能为长期使用芳香化酶抑制剂时出现的小脑功能缺陷提供解剖学基础。