Maternal Immune Activation Causes Social Behavior Deficits and Hypomyelination in Male Rat Offspring with an Autism-Like Microbiota Profile

Brain Sciences

卷:11

Jing-Huei Lai¹  Yung-Hsiao Chiang¹  Syuan-You Ye²  Gilbert Aaron Lee²  Ching-Chiung Wang³  Sung-Hui Tseng⁴  Yen-Kuang Lin⁵  Yu-Chen S. H. Yang⁶  Chia-Jung Lee⁷  Yu-Chun Lo⁸ 

[1] Core Laboratory of Neuroscience, Office of R&D, Taipei Medical University, Taipei 110, Taiwan;

[2] Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan;

[3] Department of Pharmaceutical Sciences, Taipei Medical University, Taipei 110, Taiwan;

[4] Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, No. 250 Wu Hsing Street, Taipei 110, Taiwan;

[5] Graduate Institute of Athletics and Coaching Science, National Taiwan Sport University, Taoyuan 333, Taiwan;

[6] Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan;

[7] PhD Program for Clinical Drug Discovery of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan;

[8] PhD Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan;

关键词: autism spectrum disorder;    lipopolysaccharide;    maternal immune activation;    microbiota;    three-chamber test;    myelination;   

DOI  :  10.3390/brainsci11081085

来源: DOAJ

【 摘 要 】

Maternal immune activation (MIA) increases the risk of autism spectrum disorder (ASD) in offspring. Microbial dysbiosis is associated with ASD symptoms. However, the alterations in the brain–gut–microbiota axis in lipopolysaccharide (LPS)-induced MIA offspring remain unclear. Here, we examined the social behavior, anxiety-like and repetitive behavior, microbiota profile, and myelination levels in LPS-induced MIA rat offspring. Compared with control offspring, MIA male rat offspring spent less time in an active social interaction with stranger rats, displayed more anxiety-like and repetitive behavior, and had more hypomyelination in the prefrontal cortex and thalamic nucleus. A fecal microbiota analysis revealed that MIA offspring had a higher abundance of Alistipes, Fusobacterium, and Ruminococcus and a lower abundance of Coprococcus, Erysipelotrichaies, and Actinobacteria than control offspring, which is consistent with that of humans with ASD. The least absolute shrinkage and selection operator (LASSO) method was applied to determine the relative importance of the microbiota, which indicated that the abundance of Alistipes and Actinobacteria was the most relevant for the profile of defective social behavior, whereas Fusobacterium and Coprococcus was associated with anxiety-like and repetitive behavior. In summary, LPS-induced MIA offspring showed an abnormal brain–gut–microbiota axis with social behavior deficits, anxiety-like and repetitive behavior, hypomyelination, and an ASD-like microbiota profile.

【 授权许可】

Unknown