Maternal omega-3 fatty acid supplementation against prenatal lead exposure induced cognitive impairment in offspring mice

• Published in: Journal of toxicological sciences 2022, Vol.47(5), pp.183-192
• Main Authors: Shao, Jing, Wang, Shuli, Liu, Lan
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; BDNF/TrkB/CREB signaling; Bioassays; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive impairment; Cyclic AMP; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - genetics; Dietary Supplements; Enzyme-linked immunosorbent assay; Exposure; Fatty acids; Fatty Acids, Omega-3 - therapeutic use; Female; Fetuses; Field tests; Heme; Heme oxygenase (decyclizing); Hippocampus - metabolism; Impairment; Kinases; Lead - toxicity; Lead poisoning; Maze Learning; Memory; Mice; mRNA; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Offspring; Omega-3 fatty acid; Open-field behavior; Oxidants; Oxidizing agents; Oxygenase; Pregnancy; Prenatal experience; Prenatal Exposure Delayed Effects - prevention & control; Prenatal lead exposure; Protein-tyrosine kinase; Proteins; Receptor, trkB - genetics; Receptor, trkB - metabolism; Receptor, trkB - pharmacology; RNA, Messenger - metabolism; Short term memory; Signal Transduction; Spatial discrimination learning; Spatial memory; Superoxide Dismutase - metabolism; Supplements; TrkB receptors; Tyrosine
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.47.183

Maternal lead exposure is associated with poor outcomes in fetal brain development such as cognitive dysfunction. Here, we aimed to reveal the effect and mechanism of omega-3 fatty acids in ameliorating maternal lead exposure-induced cognitive impairment in mouse offspring. The activity levels of locomotor and anxiety, memory and learning capacity, spatial working memory, and cognitive behavioral function were determined using the open field test, Morris water maze, Y-maze, and nest-building test, respectively. The protein levels of brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay or Western blot. The mRNA levels of BDNF, tyrosine kinase B (TrkB) and cyclic AMP response element binding protein (CREB) were measured by real-time qPCR. Malondialdehyde (MDA) and anti-oxidants, including SOD, GSH and CAT, were measured using bioassay kits. We found that supplementing omega-3 significantly improved cognitive behavioral function in offspring after prenatal lead exposure. The protein and mRNA levels of BDNF, TrkB and CREB in the prenatal lead exposure group were significantly upregulated by omega-3 supplementation. The MDA level in the prenatal lead exposure group was markedly elevated compared with the control group, which was significantly reduced by omega-3. Omega-3 restored anti-oxidants SOD, GSH and CAT to control levels after prenatal lead exposure. Omega-3 significantly upregulated Nrf2 nuclear expression and HO-1 expression after prenatal lead exposure. Overall, omega-3 supplementation significantly elevated the BDNF/TrkB/CREB pathway and restores anti-oxidants by upregulating the Nrf2/HO-1, thereby improving cognitive function in offspring after prenatal lead exposure.