| Background: Based on the developmental origin for health and disease(DOHaD)theory people experience adverse events in early stage of life was relate to adult chronic disease.Epidemiological studies have shown that early malnutrition can cause cognitive dysfunction after years,but the specific mechanism is not clear.Objective:To investigate the effect of early malnutrition on cognitive function in adult stage through induces microglia-induced neuroinflammation.Methods:The SD rats were modeled of early malnutrition.Some of offspring were given supplement of n3-polyunsaturated fatty acid(n3-PUFA)after lactation.Weight of newborn rats was measured to assess the nutritional status.The ability of learning and memory of offspring rats were assayed by Morris water maze and the fear conditioning.The expression of microglia marker Ionized calcium binding adapter molecule-1(Iba-1)in the hippocampus were detected by Immunohistochemistry.Real-time quantitative PCR and Western blot were used to assay the expression of microglia M1 markers iNOS,COX-2 in the hippocampus.The expression of IL-1β,TNF-α,IL-6,IL-4,IL-1ra and TGF-β mRNA in hippocampus were detected by RT-qPCR.Results:The early malnutrition group was born with lower birth weight(P<0.001).After postnatal 3 months,the ability of learning and memory was reduced(P<0.05),the expression of iNOS was increased both in mRNA and protein(P<0.05),the expression of Iba-1 was increased(P<0.05),the expression of pro-inflammatory mediators was increased(P<0.05)and the anti-inflammatory mediators expression was decreased(P<0.05).Supplementation of n3-PUFA could alleviate microglia-mediated inflammatory response.Conclusion: Early malnutrition may impair the cognitive function of adult offspring,which may be related to the neuroinflammation induced by activating microglia in hippocampus. |
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