Early-life adversity induces metabolic alterations in a rodent model of depression: a differential stress response perspective.

IF 2.5 4区医学 Q3 NEUROSCIENCES

Acta Neuropsychiatrica Pub Date : 2026-03-05 DOI:10.1017/neu.2026.10066

Daniël J van Rensburg, Zander Lindeque, Ashleigh Jade Whitney, Stephan F Steyn

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引用次数: 0

Abstract

Objective: Investigating metabolic differences between pre-pubertal Flinders sensitive (FSL) and resistant (FRL) line rats and determine the impact of early-life adversity on these differences.

Methods: Untargeted metabolomic profiling of whole-brain tissue from postnatal day 25 Flinders line rats, exposed to maternal separation with early weaning (MSEW), or not, was done by using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS).

Results: Irrespective of MSEW, FSL rats had higher urea and lower glutamine, norvaline and valine concentrations than age-matched FRL controls. Across strains, MSEW reduced gamma-aminobutyric acid (GABA), glutamate, glutamine, lactate, phenylalanine, norvaline and valine concentrations, whist elevating 2-keto-3-methylbutyric acid, glycerophosphate, and urea. This effect was most pronounced in FRL rats.

Conclusion: Pre-pubertal FSL rats displayed distinct metabolic signatures associated with altered energy and amino acid metabolism. Early-life stress further disrupts these pathways, highlighting key metabolites as potential targets in the expansion of the biological constructs underlying the pre-pubertal FSL/FRL model.

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早期生活逆境诱导代谢改变的啮齿动物模型的抑郁症：差异应激反应的角度。

目的：探讨青春期前弗林德斯敏感系（FSL）和抗性系（FRL）大鼠代谢差异，并探讨早期逆境对这些差异的影响。方法：采用气相色谱-飞行时间质谱（GC-TOF-MS）对25只弗林德斯系大鼠的全脑组织进行非靶向代谢组学分析，这些大鼠分别暴露于母体早期断奶分离（MSEW）或未暴露于母体早期断奶分离（MSEW）。结果：与年龄匹配的FRL对照组相比，FSL大鼠的尿素含量较高，谷氨酰胺、正缬氨酸和缬氨酸浓度较低。在所有菌株中，MSEW降低了γ -氨基丁酸（GABA）、谷氨酸、谷氨酰胺、乳酸、苯丙氨酸、正缬氨酸和缬氨酸的浓度，同时升高了2-酮-3-甲基丁酸、甘油磷酸盐和尿素的浓度。这种效果在FRL大鼠中最为明显。结论：青春期前FSL大鼠表现出与能量和氨基酸代谢改变相关的独特代谢特征。早期生活压力进一步破坏了这些途径，突出了关键代谢物作为青春期前FSL/FRL模型基础生物契约扩展的潜在目标。

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

Acta Neuropsychiatrica NEUROSCIENCES-PSYCHIATRY

自引率

5.30%

发文量

期刊介绍： Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.