The interplay between oxidative stress and inflammation supports autistic-related behaviors in Cntnap2 knockout mice

被引：0

作者：

Pangrazzi, Luca ^{[1
,2
]}

Cerilli, Enrica ^{[1
]}

Balasco, Luigi ^{[1
,10
]}

Khurshid, Chrow ^{[3
,4
]}

Tobia, Caterina ^{[1
]}

Dall 'O', Ginevra Matilde ^{[1
]}

Chelini, Gabriele ^{[1
,9
]}

Perini, Samuel ^{[5
]}

Filosi, Michele ^{[5
]}

Barbieri, Anna ^{[5
]}

Ravizza, Teresa ^{[6
]}

Vezzani, Annamaria ^{[6
]}

Provenzano, Giovanni ^{[5
]}

Pastore, Anna ^{[7
]}

Weinberger, Birgit ^{[2
]}

Rubert, Josep ^{[3
]}

Domenici, Enrico ^{[5
,8
]}

Bozzi, Yuri ^{[1
,9
]}

机构：

[1] Univ Trento, CIMeC Ctr Mind Brain Sci, Piazza Manifattura 1, I-38068 Trento, Italy

[2] Univ Innsbruck, Inst Biomed Aging Res, Rennweg 10, A-6020 Innsbruck, Austria

[3] Wageningen Univ & Res, Div Human Nutr & Hlth, Wageningen, Netherlands

[4] Univ Kirkuk, Coll Agr, Kirkuk, Iraq

[5] Univ Trento, Dept Cellular Computat & Integrat Biol CIBIO, Via Sommar 9, I-38123 Trento, Italy

[6] IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Milan, Italy

[7] Bambino GesuChildrens Hosp, Metabol & Prote Unit, IRCCS, Rome, Italy

[8] Univ Trento, Fdn Microsoft Res, Ctr Computat & Syst Biol COSBI, I-38068 Rovereto, Trento, Italy

[9] CNR Neurosci Inst, I-56124 Pisa, Italy

[10] Univ Cattolica Sacro Cuore, Dept Life Sci & Publ Hlth, I-00168 Rome, Italy

来源：

BRAIN BEHAVIOR AND IMMUNITY | 2025年 / 127卷

关键词：

Autism; ASD; Inflammation; ROS; Microglia; N-ACETYLCYSTEINE; CEREBELLAR; ANTIOXIDANTS; ACTIVATION; BRAIN; CONNECTIVITY; DYSFUNCTION; EXPRESSION; MONOCYTES; RESPONSES;

D O I：

10.1016/j.bbi.2025.02.030

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental condition characterized by social communication deficits and repetitive/restricted behaviors. Several studies showed that oxidative stress and inflammation may contribute to ASD. Indeed, increased levels of oxygen radicals and pro-inflammatory molecules were described in the brain and peripheral blood of persons with ASD and mouse models. Despite this, a potential direct connection between oxidative stress and inflammation within specific brain areas and ASDrelated behaviors has not been investigated in detail yet. Here, we used RT-qPCR, RNA sequencing, metabolomics, immunohistochemistry, and flow cytometry to show that pro-inflammatory molecules were increased in the cerebellum and periphery of mice lacking Cntnap2, a robust model of ASD. In parallel, oxidative stress was present in the cerebellum of mutant animals. Systemic treatment with N-acetyl-cysteine (NAC) rescued cerebellar oxidative stress, inflammation, as well as motor and social impairments in Cntnap2-/- mice, concomitant with enhanced function of microglia cells in NAC-treated mutants. Intriguingly, social deficits, cerebellar inflammation, and microglia dysfunction were induced by NAC in Cntnap2+/+ animals. Our findings suggest that the interplay between oxidative stress and inflammation accompanied by genetic vulnerability may underlie ASDrelated behaviors in Cntnap2 mutant mice.

引用

页码：57 / 71

页数：15

共 77 条

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