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

International Journal of Molecular Sciences

Wenli Han¹  Peishuang Yao²  Zhe Peng²  Zhihao Chen²  Yuke Li²  Yang Yang²  Ying Luo²  Haifeng Huang²  Xiaodan Tan²  Jiahua Zhang²  Huan Li²  Hui Xia²  Congli Hu²  Junqing Yang²  Lu Yang²  Hong Wang²  Qi Chen²  Miaomiao Li² 

[1] Animal Laboratory Center, Chongqing Medical University, Chongqing 400016, China;Department of Pharmacology, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China;

关键词: prenatal maternal inflammation;    lipopolysaccharide;    central nervous system inflammation;    cyclooxygenase-2;    DPs;   

DOI  :  10.3390/ijms23116142

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown