阿尔茨海默病 3xTg 小鼠模型中下丘脑线粒体生物能和炎症相关信号的改变与年龄和性别有关。

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Aida Adlimoghaddam, Kyle M Fontaine, Benedict C Albensi
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引用次数: 0

摘要

线粒体功能障碍和相关的炎症信号在衰老和阿尔茨海默病(AD)中都起着关键作用。研究还表明,下丘脑功能在阿尔茨海默病中也会受到影响。鉴于在下丘脑中观察到线粒体的改变,因此下丘脑可能是抗阿尔茨海默病药物的靶点。本研究调查了年龄和性别如何影响 3xTg 小鼠和对照组小鼠 2、6 和 13 个月时下丘脑线粒体的线粒体生物能和炎症信号转导,旨在加深我们对衰老和 AD 过程的了解。研究参数包括耗氧率、线粒体复合物 I-V 亚基的表达水平、细胞色素 c 氧化酶(COX)的酶活性、与炎症相关的转录因子(如 NF-κB、pIκB-α、Nrf2)以及其他炎症生物标志物。3xTg雌性小鼠早在2个月大时就出现了下丘脑线粒体功能障碍,但3xTg雄性小鼠直到6个月大时才出现变化。在 3xTg 小鼠中,线粒体复合物 I-II 亚基的表达水平在雌雄小鼠中均显著降低。在 13 个月大时,还观察到 COX 活性存在明显的性别差异,雌性 COX 活性低于雄性。此外,在正常衰老和AD进展过程中,不同年龄组的NF-κB、pIκB-α、Nrf2和其他炎症生物标志物也存在明显的性别差异。这些发现突显了下丘脑生物能和炎症的重要性别差异,为预防和/或治疗老年痴呆症提供了潜在的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Age- and sex-associated alterations in hypothalamic mitochondrial bioenergetics and inflammatory-associated signaling in the 3xTg mouse model of Alzheimer's disease.

Mitochondrial dysfunction and associated inflammatory signaling are pivotal in both aging and in Alzheimer's disease (AD). Studies have also shown that hypothalamic function is affected in AD. The hypothalamus may be a target for AD drugs given that mitochondrial alterations are observed in the hypothalamus. This study investigated how age and sex affect mitochondrial bioenergetics and inflammatory signaling in the hypothalamic mitochondria of 3xTg and control mice at 2, 6, and 13 months, aiming to enhance our understanding of these processes in aging and AD. Parameters included oxygen consumption rates, expression levels of subunits comprising mitochondrial complexes I-V, the enzymatic activity of cytochrome c oxidase (COX), transcription factors associated with inflammation such as NF-κB, pIκB-α, Nrf2, and other inflammatory biomarkers. Hypothalamic mitochondrial dysfunction was observed in 3xTg females as early as 2 months, but no changes were detected in 3xTg males until 6 months of age. In 3xTg mice, subunit expression levels for mitochondrial complexes I-II were significantly reduced in both sexes. Significant sex-based differences in COX activity were also observed at 13 months of age, with levels being lower in females compared to males. In addition, significant sex differences were indicated in NF-κB, pIκB-α, Nrf2, and other inflammatory biomarkers at different age groups during normal aging and AD progression. These findings highlight important sex differences in hypothalamic bioenergetics and inflammation, offering insights into potential new targets for preventing and/or treating AD.

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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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