Docosahexaenoic acid improves cognition and hippocampal pyroptosis in rats with intrauterine growth restriction

Lijia Wan; Xiaori He; Mingfeng He; Yuanqiang Yu; Weiming Jiang; Can Liang; Kaiju Luo; Xiaoyun Gong; Yonghui Yang; Qingyi Dong; Pingyang Chen

doi:10.1016/j.heliyon.2023.e12920

Docosahexaenoic acid improves cognition and hippocampal pyroptosis in rats with intrauterine growth restriction

Heliyon. 2023 Jan 27;9(2):e12920. doi: 10.1016/j.heliyon.2023.e12920. eCollection 2023 Feb.

Authors

Lijia Wan^{1

2}, Xiaori He^{1

3}, Mingfeng He^{1

3}, Yuanqiang Yu^{1

3}, Weiming Jiang⁴, Can Liang^{1

3}, Kaiju Luo^{1

3}, Xiaoyun Gong^{1

3}, Yonghui Yang^{1

3}, Qingyi Dong^{1

3}, Pingyang Chen^{1

3}

Affiliations

¹ Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
² Department of Child Healthcare, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410011, PR China.
³ Laboratory of Neonatal Disease, Institute of Pediatrics, Central South University, Changsha, Hunan 410011, PR China.
⁴ Children's Institute of Three Gorges University, Yichang Central People's Hospital, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443003, PR China.

Abstract

Background and objective: Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its genetic growth potential in utero resulted by maternal, placental, fetal, and genetic factors. Previous studies have reported that IUGR is associated with a high incidence of neurological damage, although the precise causes of such damage remain unclear. We aimed to investigate whether cognitive impairment in rats with IUGR is related to pyroptosis of hippocampal neurons and determine the effect of early intervention with docosahexaenoic acid (DHA).

Methods: Learning and memory function was assessed using the Morris water maze test. The morphological structure and ultrastructure of the hippocampus was examined via hematoxylin and eosin staining and electron microscopy respectively. The pyroptosis of hippocampal neuron was detected by gasdermin-D (GSDMD) immunofluorescence staining, mRNA and protein expression of nuclear localization leucine-rich-repeat protein 1 (NLRP1), caspase-1, GSDMD, and quantification of inflammatory cytokines interleukin (IL)-1β and IL-18 in the hippocampus.

Results: IUGR rats exhibited decreased learning and memory function, morphological structure and ultrastructural changes in hippocampus compared to controls. IUGR rats also exhibited increased hippocampal quantification of GSDMD immunofluorescence staining, increased mRNA and protein expression of NLRP1, caspase-1, and GSDMD, and increased quantification of IL-1β and IL-18 in the hippocampus. Intervention with DHA attenuated these effects.

Conclusion: Cognitive impairment in rats with IUGR may be related to pyroptosis of hippocampal neurons. Early intervention with DHA may attenuate cognitive impairment and reduce hippocampal pyroptosis in rats with IUGR.

Keywords: Cognitive impairment; DHA; Hippocampus; Intrauterine growth restriction; Pyroptosis; Small for gestational age.