Endocrine Abstracts (2017) 49 GP156 | DOI: 10.1530/endoabs.49.GP156

Liraglutide treatment prevented the increased expression of proinflammatory cytokines in the hippocampus of male pups in a perinatal stress model of food restriction

Yolanda Diz-Chaves1, Laura Toba1, Juan Fandiño1, Lucas González-Matías1, Luis Miguel Garcia-Segura2 & Federico Mallo1

1University of Vigo, CINBIO, Vigo, Spain; 2CSIC, Instituto Cajal, Madrid, Spain.

Adverse events during gestation in rodents, results in an enhancement of immune function, including elevated levels of inflammatory cytokines in the brain. Liraglutide is a GLP-1 receptor agonists known to exert neuroprotective effects in brain. The aim of this study was to elucidate if liraglutide given to food restricted (FR) pregnant rats may prevent the deleterious effects of FR in the hippocampal inflammatory status of male and female pups at 21 days of age (D21). 20 Sprague-Dawley pregnant rats were included. Controls (CT) were fed ad libitum, whereas dams in restricted group were fed with 50% (50FR) daily intake of control dams. Pregnant rats were treated with liraglutide (100 μg/kg per 12 h; 50FR/LIR, CT/LIR) or vehicle (50FR/VEH, CT/VEH) from gestational day 14 to 21. During lactation FR was increased to 30%. At D21 and before weaning, pups were sacrificed. The hippocampi were obtained and stored at −80 °C until analysis. mRNA expression levels of IL1β, IL6,NFKβ,IL 10 and Arginase1 in the hippocampus were assessed by RT-PCR. Immunohistochemistry analysis for Iba1 (marker of microglia) was performed in dentate gyrus (DG). The FR-mothers model promoted a proinflammatory state in the hippocampus just in male but not in female pups. 50FR male rats displayed increased mRNA expression of IL1β, IL6 and NFKβ compared to control males. LIR treatment decreased the expression of these cytokines and increased IL6 in control males. Furthermore, LIRA treatment increased the anti-inflammatory cytokine IL10 in 50FR male and CT female rats and the mRNA expression of the arginase1 (marker of microglia M2-like phenotype) in 50FR male rats. The number of IBA1 immunopositive cells were increased in the DG of 50FR males compared to controls, and were reduced by the treatment with LIRA. In conclusion, LIRA prevents the proinflammatory status induced by FR of the mother in male pups and enhanced anti-inflammatory markers.

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