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抽动障碍大鼠皮质-纹状体-丘脑-皮质回路的代谢异常

Metabolic abnormalities of the cortico‑striato‑thalamo‑cortical circuit of rats with tic disorder.

作者信息

Yu Jingru, Su Jiateng, Yu Guo, Zhang Zhongyang, Wu Yue, Xiao Gong, Zhang Xin, Hao Juanjuan

机构信息

School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China.

Science and Education Department, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.

出版信息

Mol Med Rep. 2025 Aug;32(2). doi: 10.3892/mmr.2025.13592. Epub 2025 Jun 13.

DOI:10.3892/mmr.2025.13592
PMID:40511541
Abstract

Tic disorder (TD) is a developmental neuropsychiatric disorder that primarily occurs during childhood and impacts the quality of life and psychosocial function of patients. The pathogenesis of TD involves the dysregulation of the cortico‑striato‑thalamo‑cortical (CSTC) circuit and metabolic abnormalities may serve an important role. The aim of the present study was to detect and analyze the metabolic abnormalities in the CSTC circuit in TD, providing a reference value for the study of its pathogenesis. A total of 10 male Wistar rats were randomly divided into the control (CK) group (n=5) and the TD group (n=5). Each rat received a daily intraperitoneal injection of 0.9% saline or 3,3'‑iminodipropionitrile for 7 consecutive days. Tissues were collected from the striatum and cortex, and ultra‑performance liquid chromatography‑tandem mass spectrometry was used to measure metabolite concentrations in the brain tissue samples. Significant differences in the metabolites and metabolic pathways of the CK and TD groups were observed. In the striatum, 13 differentially present metabolites were observed between the CK group and TD group, while 21 differentially present metabolites were identified in the cortex. In the CSTC circuit, the common significantly differentially present metabolites were progesterone, corticosterone, deoxycorticosterone, 11‑dehydrocorticosterone, chenodeoxycholic acid and hyodeoxycholic acid. The common differentially present metabolic pathways were 'steroid hormone biosynthesis' and 'aldosterone synthesis and secretion'. Notably, the abnormality of the 'tryptophan metabolism' pathway was only present in the cortex. These results indicated that there were metabolic abnormalities in the CSTC circuit in TD. The most significantly differentially present metabolite was progesterone. 'Steroid hormone biosynthesis' and 'aldosterone synthesis and secretion' were the significantly altered metabolic pathways in TD.

摘要

抽动障碍(TD)是一种主要发生在儿童期的发育性神经精神障碍,会影响患者的生活质量和心理社会功能。TD的发病机制涉及皮质-纹状体-丘脑-皮质(CSTC)回路的失调,代谢异常可能起重要作用。本研究的目的是检测和分析TD患者CSTC回路中的代谢异常,为其发病机制的研究提供参考价值。将10只雄性Wistar大鼠随机分为对照组(CK组,n = 5)和TD组(n = 5)。每只大鼠连续7天每天腹腔注射0.9%生理盐水或3,3'-亚氨基二丙腈。从纹状体和皮质收集组织,采用超高效液相色谱-串联质谱法测量脑组织样本中的代谢物浓度。观察到CK组和TD组在代谢物和代谢途径上存在显著差异。在纹状体中,CK组和TD组之间观察到13种差异表达的代谢物,而在皮质中鉴定出21种差异表达的代谢物。在CSTC回路中,共同的显著差异表达代谢物是孕酮、皮质酮、脱氧皮质酮、11-脱氢皮质酮、鹅去氧胆酸和猪去氧胆酸。共同的差异表达代谢途径是“类固醇激素生物合成”和“醛固酮合成与分泌”。值得注意的是,“色氨酸代谢”途径的异常仅存在于皮质中。这些结果表明TD患者的CSTC回路存在代谢异常。差异表达最显著的代谢物是孕酮。“类固醇激素生物合成”和“醛固酮合成与分泌”是TD中显著改变的代谢途径。

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New insights of metabolite abnormalities in the thalamus of rats with iminodiproprionitrile-induced tic disorders.亚氨基二丙腈诱导抽动障碍大鼠丘脑代谢物异常的新见解。
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Chronic stress promotes basal ganglia disinhibition by increasing the excitatory drive of direct-pathway neurons.
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Hair Cortisol and Perceived Stress-Predictors for the Onset of Tics? A European Longitudinal Study on High-Risk Children.头发皮质醇与感知压力——抽动症发作的预测因素?一项针对高危儿童的欧洲纵向研究。
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