Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring
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 in...
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MDPI AG
2023-06-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/6/958 |
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| author | Fang Lin Xinyuan Wang Ruifang Luo Binlin Yuan Shasha Ye Ting Yang Lu Xiao Jie Chen |
| author_facet | Fang Lin Xinyuan Wang Ruifang Luo Binlin Yuan Shasha Ye Ting Yang Lu Xiao Jie Chen |
| author_sort | Fang Lin |
| collection | DOAJ |
| description | 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-HT<sub>1B</sub>R) 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. |
| first_indexed | 2024-03-11T02:40:59Z |
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| last_indexed | 2024-03-11T02:40:59Z |
| publishDate | 2023-06-01 |
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| series | Brain Sciences |
| spelling | doaj.art-a9bbd55f8ba445be8a9982251435fd9d2023-11-18T09:36:56ZengMDPI AGBrain Sciences2076-34252023-06-0113695810.3390/brainsci13060958Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young OffspringFang Lin0Xinyuan Wang1Ruifang Luo2Binlin Yuan3Shasha Ye4Ting Yang5Lu Xiao6Jie Chen7Chongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaChongqing Key Laboratory of Childhood Nutrition and Health, Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University, Chongqing 400015, ChinaAutism 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-HT<sub>1B</sub>R) 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.https://www.mdpi.com/2076-3425/13/6/958serotonin (5-HT)tryptophan metabolismmedial prefrontal cortex (mPFC)autism spectrum disorder (ASD)lipopolysaccharide (LPS) |
| spellingShingle | Fang Lin Xinyuan Wang Ruifang Luo Binlin Yuan Shasha Ye Ting Yang Lu Xiao Jie Chen Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring Brain Sciences serotonin (5-HT) tryptophan metabolism medial prefrontal cortex (mPFC) autism spectrum disorder (ASD) lipopolysaccharide (LPS) |
| title | Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring |
| title_full | Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring |
| title_fullStr | Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring |
| title_full_unstemmed | Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring |
| title_short | Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring |
| title_sort | maternal lps exposure enhances the 5 ht level in the prefrontal cortex of autism like young offspring |
| topic | serotonin (5-HT) tryptophan metabolism medial prefrontal cortex (mPFC) autism spectrum disorder (ASD) lipopolysaccharide (LPS) |
| url | https://www.mdpi.com/2076-3425/13/6/958 |
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