Neuroinflammatory Pathways in Autism Spectrum Disorder: Unraveling the Role of Sirtuin 1 in Clinical Samples

IF 2.3 4区医学 Q2 DEVELOPMENTAL BIOLOGY

Developmental Neurobiology Pub Date : 2025-08-29 DOI:10.1002/dneu.22981

Merve Cikili-Uytun, Esra Yurumez, Banu Kaymak, Ozlem Dogan, Humeyra Hilal Ozturk, Beyza Nur Baysar Kanoglu, Didem Behice Oztop

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引用次数: 0

Abstract

Despite extensive research, the etiological factors contributing to autism spectrum disorder (ASD) remain incompletely understood, with potential influences ranging from genetic predispositions to environmental factors. Sirtuin 1 (SIRT1), an NAD⁺-dependent histone deacetylase involved in mitigating oxidative stress and its association with other neurodevelopmental disorders, explores its function in ASD. This study aimed to elucidate the relationship between SIRT1 and inflammatory cytokines, specifically interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), in patients with ASD.

This study enrolled 46 children diagnosed with ASD and 44 typically developing (TD) children aged 36–120 months. Diagnosis of ASD was confirmed using DSM-5 criteria through clinical and observational assessments conducted by three experienced child and adolescent psychiatrists at the outpatient Infant Mental Health unit of Ankara University. The Childhood Autism Rating Scale (CARS) and the Repetitive Behavior Scale-Revised (RBS-R) were used to assess autistic behaviors.

Analysis of serum levels of SIRT1, IL-6, and TNF-α revealed no significant differences between the ASD group and the TD group. Correlation analysis demonstrated a significant positive relationship between SIRT1 levels and IL-6 (r = 0.71, p < 0.001) and TNF-α (r = 0.86, p < 0.001). Additionally, regression phenomena exhibited a moderate negative correlation with IL-6 (r = −0.32, p = 0.02) and TNF-α (r = −0.38, p = 0.008). Age was positively correlated with levels of IL-6, TNF-α, and SIRT1. However, no correlations were found between these parameters and gender.

These findings do not support the hypothesized role of disturbances in the expression of circulating cytokines and SIRT1 as indicators of systemic inflammation in autism. Further longitudinal studies should examine these immune markers in blood samples from large sample sizes.

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自闭症谱系障碍的神经炎症途径：揭示Sirtuin 1在临床样本中的作用

尽管进行了广泛的研究，但导致自闭症谱系障碍（ASD）的病因仍不完全清楚，其潜在影响范围从遗传易感性到环境因素。SIRT1是一种NAD+依赖性组蛋白去乙酰化酶，参与减轻氧化应激及其与其他神经发育障碍的关联，研究其在ASD中的功能。本研究旨在阐明SIRT1与ASD患者炎症因子，特别是白细胞介素6 （IL-6）和肿瘤坏死因子α (TNF-α)之间的关系。这项研究招募了46名被诊断为ASD的儿童和44名年龄在36-120个月之间的典型发育（TD）儿童。通过由安卡拉大学门诊婴儿心理健康部门的三名经验丰富的儿童和青少年精神病学家进行的临床和观察性评估，使用DSM-5标准确诊ASD。采用儿童自闭症评定量表（CARS）和重复行为量表-修订版（RBS-R）评估自闭症行为。血清SIRT1、IL-6、TNF-α水平分析显示，ASD组与TD组之间无显著差异。相关分析显示SIRT1水平与IL-6 （r = 0.71, p < 0.001）和TNF-α (r = 0.86, p < 0.001)呈正相关。此外，回归现象显示IL-6 （r = - 0.32, p = 0.02）和TNF-α (r = - 0.38, p = 0.008)呈中度负相关。年龄与IL-6、TNF-α、SIRT1水平呈正相关。然而，这些参数与性别之间没有相关性。这些发现不支持循环细胞因子和SIRT1表达紊乱作为自闭症全身性炎症指标的假设作用。进一步的纵向研究应该从大样本量的血液样本中检查这些免疫标记物。

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

Developmental Neurobiology 生物-发育生物学

CiteScore

6.50

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Developmental Neurobiology (previously the Journal of Neurobiology ) publishes original research articles on development, regeneration, repair and plasticity of the nervous system and on the ontogeny of behavior. High quality contributions in these areas are solicited, with an emphasis on experimental as opposed to purely descriptive work. The Journal also will consider manuscripts reporting novel approaches and techniques for the study of the development of the nervous system as well as occasional special issues on topics of significant current interest. We welcome suggestions on possible topics from our readers.