Maternal Prenatal Inflammation Increases Brain Damage Susceptibility of Lipopolysaccharide in Adult Rat Offspring via COX-2/PGD-2/DPs Pathway Activation.

Abstract

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer's disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aβ, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aβ, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.

• Authors: Jiahua Zhang, Peishuang Yao, Wenli Han, Ying Luo, Yuke Li, Yang Yang, Hui Xia, Zhihao Chen, Qi Chen, Hong Wang, Lu Yang, Huan Li, Congli Hu, Haifeng Huang, Zhe Peng, Xiaodan Tan, Miaomiao Li, Junqing Yang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 11 (May 30 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35682823 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• Transcription Factors
• Cyclooxygenase 2
• Meloxicam

Topics

• Animals
• Brain (metabolism)
• Brain Injuries (metabolism)
• Cyclooxygenase 2 (metabolism)
• Female
• Humans
• Inflammation (metabolism)
• Lipopolysaccharides (pharmacology)
• Meloxicam
• Memory Disorders (metabolism)
• Necrosis (metabolism)
• Pregnancy
• Preimplantation Diagnosis
• Prenatal Exposure Delayed Effects (metabolism)
• Rats
• Transcription Factors (metabolism)