Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice

Hai-Long Zhang; Shufen Hu; Shu-Ting Qu; Meng-Dan Lv; Jun-Jun Wang; Xin-Ting Liu; Jia-He Yao; Yi-Yan Ding; Guang-Yin Xu

doi:10.3390/cimb46030121

Current Issues in Molecular Biology (Feb 2024)

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice

Hai-Long Zhang,
Shufen Hu,
Shu-Ting Qu,
Meng-Dan Lv,
Jun-Jun Wang,
Xin-Ting Liu,
Jia-He Yao,
Yi-Yan Ding,
Guang-Yin Xu

Affiliations

Hai-Long Zhang: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Shufen Hu: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Shu-Ting Qu: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Meng-Dan Lv: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Jun-Jun Wang: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Xin-Ting Liu: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Jia-He Yao: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Yi-Yan Ding: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China
Guang-Yin Xu: Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Suzhou Medical College of Soochow University, Medical Center of Soochow University, Suzhou 215123, China

DOI: https://doi.org/10.3390/cimb46030121
Journal volume & issue: Vol. 46, no. 3
pp. 1851 – 1864

Abstract

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Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring’s PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

Published in Current Issues in Molecular Biology

ISSN: 1467-3037 (Print); 1467-3045 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.mdpi.com/journal/cimb

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