Related Experiment Video
Updated: Jul 25, 2025
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring
Fang Lin1,2, Xinyuan Wang1,2, Ruifang Luo1,2
1Chongqing Key Laboratory of Childhood Nutrition and Health, Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400015, China.
Insights
Maternal exposure to lipopolysaccharide (LPS) in rats induced autism-like behaviors and increased serotonin (5-HT) in the offspring's medial prefrontal cortex (mPFC). This may be linked to altered 5-HT metabolism in the colon.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Autism spectrum disorder (ASD) is a neurodevelopmental condition impacting social interaction and communication.
- Maternal immune activation, such as lipopolysaccharide (LPS) exposure, is a proposed risk factor for ASD development.
- Serotonin (5-HT) system alterations are implicated in ASD pathophysiology.
Purpose of the Study:
- To investigate the impact of maternal LPS exposure on serotonin levels and related gene expression in the medial prefrontal cortex (mPFC) of offspring.
- To explore the relationship between maternal LPS exposure, autism-like behaviors, and alterations in tryptophan and serotonin metabolism.
- To examine the role of the colon's serotonin system in mediating these effects.
Main Methods:
- Establishment of an autism-like rat model via maternal intraperitoneal LPS injection.
- Behavioral assessment of offspring for autism-like phenotypes.
- RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs) in the mPFC.
- Measurement of serotonin (5-HT) levels in the mPFC, serum, and colon.
- Analysis of gene and protein expression related to serotonin synthesis, metabolism, and receptors (TPH1, TPH2, SERT, 5-HT1BR).
- Golgi-Cox staining to evaluate neuronal morphology in the mPFC.
Main Results:
- Maternal LPS exposure induced autism-like behaviors in offspring.
- Offspring exhibited significantly increased serotonin (5-HT) levels in the mPFC.
- RNA-seq revealed enrichment of pathways related to tryptophan metabolism and the serotonin system.
- Alterations in tryptophan and serotonin metabolism were observed, with reduced 5-HT catabolic enzyme mRNA.
- Increased 5-HT1BR expression in the mPFC, but no changes in TPH2 or SERT.
- Elevated 5-HT concentrations in serum and colon, with increased TPH1 and reduced SERT in the colon.
- Reduced neuronal dendritic length and spine density in the mPFC of LPS-exposed offspring.
Conclusions:
- Maternal LPS exposure leads to elevated serotonin (5-HT) in the medial prefrontal cortex (mPFC) of young rats with autism-like behaviors.
- These neurochemical changes may be partly driven by abnormal serotonin metabolism in the colon.
- The findings highlight a potential link between maternal immune activation, gut-brain axis, and ASD-related neurodevelopmental alterations.
Abstract:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by reduced social interactions, impaired communication, and stereotyped behavior. The aim of this research is to investigate the changes in serotonin (5-HT) in the medial prefrontal cortex (PFC) of autism-like offspring induced by maternal lipopolysaccharide (LPS) exposure. Pregnant Sprague-Dawley rats were intraperitoneally injected with LPS to establish an autism-like model in their offspring. Offspring prenatally exposed to LPS showed autism-like behavior. The serotonin level in the mPFC of 2-week-old offspring was noticeably increased after maternal LPS exposure. Differentially expressed genes (DEGs) were enriched in pathways related to tryptophan metabolism and the serotonin system, as shown in RNA-seq findings. Consistently, tryptophan and serotonin metabolisms were altered in 2-week-old LPS-exposed offspring. The mRNA expression levels of 5-HT catabolic enzymes were remarkably reduced or tended to decrease. Moreover, maternal LPS exposure resulted in a higher serotonin 1B receptor (5-HT1BR) expression level in the mPFC but no difference in tryptophan hydroxylase 2 (TPH2) or serotonin reuptake transporter (SERT). The concentrations of 5-HT in serum and colon were increased in LPS-exposed offspring. Meanwhile, the expression level of tryptophan hydroxylase 1 (TPH1) in the colon was increased after maternal LPS treatment, whereas SERT was reduced. Furthermore, Golgi-Cox staining showed that neuronal dendritic length and spine density were significantly reduced in the mPFC of LPS-exposed offspring. The current study reveals that maternal LPS treatment resulted in an exaltation of the 5-HT of mPFC in ASD-like young rats, which may partly be caused by the abnormal elevation of 5-HT metabolism in its colon.
More Related Videos
09:09Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using PolyI:C to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
04:20Author Spotlight: Exploring Microglial Interactions with Stress-Response Circuitry Using the Limited Bedding and Nesting Model
Published on: July 12, 2024
