2. Academic Validation
  3. Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring

Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring

  • Brain Sci. 2023 Jun 15;13(6):958. doi: 10.3390/brainsci13060958.
Fang Lin 1 2,  Xinyuan Wang 1 2,  Ruifang Luo 1 2,  Binlin Yuan 1 2,  Shasha Ye 1 2,  Ting Yang 1 2,  Lu Xiao 1 2 3,  Jie Chen 1 2
Affiliations

Affiliations

  • 1 Chongqing Key Laboratory of Childhood Nutrition and Health, Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400015, China.
  • 2 Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing 400015, China.
  • 3 Department of Gastroenterology, Children's Hospital of Chongqing Medical University, Chongqing 400015, China.
PMID: 37371436 DOI: 10.3390/brainsci13060958
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.

Keywords

autism spectrum disorder (ASD); lipopolysaccharide (LPS); medial prefrontal cortex (mPFC); serotonin (5-HT); tryptophan metabolism.

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