Middle-aged females are resistant to LPS-induced learning deficits: Sex comparison

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-01-10 DOI:10.1016/j.neulet.2024.138072

Lauren G. Singleton , Kelsey F. Thompson , Jordyn Carroll , Rachel A. Kohman

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引用次数: 0

Abstract

Preclinical data have repeatedly shown learning and memory disruption following administration of the bacterial endotoxin lipopolysaccharide (LPS). Normal aging is reported to enhance vulnerability to LPS-induced cognitive impairments. However, a limitation is the primary use of male subjects. Recent evidence indicates sex-related differences in vulnerability to LPS-induced cognitive deficits [1], [2], with young females showing resilience. Whether middle-aged females are susceptible to LPS-induced cognitive impairment is unknown. The current experiment compared associative learning in young and middle-aged male and female C57BL/6J mice following a systemic LPS challenge. While LPS impaired acquisition of the two-way active avoidance conditioning task in adult and middle-aged males, females’ learning was unaffected. The sex difference in LPS-induced cognitive impairments appears unrelated to responsivity to LPS, as males and females mount a comparable sickness-like response. Additionally, relative to males, females produce higher brain levels of interleukin-6 (IL-6) and comparable splenic IL-6 levels following LPS. These data demonstrate that female resilience to LPS-induced learning deficits persists into middle age, whereas males are vulnerable as both young and middle-aged adults. Our findings confirm the importance of considering sex as a biological variable and extend the existing literature by evaluating sex-related responsivity to LPS in middle-aged males and females.

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中年女性对lps诱导的学习缺陷有抵抗力：性别比较。

临床前数据反复显示，在使用细菌内毒素脂多糖（LPS）后，学习和记忆受到破坏。据报道，正常的衰老会增加对脂多糖诱导的认知障碍的易感性。然而，一个限制是主要使用男性受试者。最近的证据表明，对lps诱导的认知缺陷的易感性存在性别差异[1,2]，年轻女性表现出适应力。中年女性是否容易发生脂多糖诱导的认知障碍尚不清楚。本实验比较了中青年雄性和雌性C57BL/6J小鼠在系统性LPS刺激后的联想学习能力。虽然LPS对成年和中年男性双向主动回避条件反射任务的习得有影响，但对女性的学习没有影响。LPS诱导的认知障碍的性别差异似乎与对LPS的反应无关，因为男性和女性会产生类似疾病的反应。此外，与男性相比，女性在LPS后产生更高的脑白细胞介素-6 （IL-6）水平和相当的脾IL-6水平。这些数据表明，女性对lps诱导的学习缺陷的适应能力持续到中年，而男性在年轻和中年时都很脆弱。我们的研究结果证实了将性别作为一个生物学变量的重要性，并通过评估中年男性和女性对LPS的性相关反应扩展了现有文献。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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