RESUMO
Introduction Exposure to social trauma may alter engagement with both fear-related and unrelated social stimuli long after. Intriguingly, how simultaneous discrimination of social fear and safety is affected in neurodevelopmental conditions remains underexplored. The role of the neuropeptide oxytocin is established in social behaviors, and yet unexplored during such a challenge post-social trauma. Methods Using Magel2 knockout mice, an animal model of Prader Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SYS), we tested memory of social fear and safety after a modified social fear conditioning task. Additionally, we tracked the activity of oxytocin neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus by fibre photometry, as animals were simultaneously presented with a choice between a fear and safe social cue during recall. Results Male Magel2 KO mice trained to fear females with electrical footshocks avoided both unfamiliar females and males during recalls, lasting even a week post-conditioning. On the contrary, trained Magel2 WT avoided only females during recalls, lasting days rather than a week post-conditioning. Inability to overcome social fear and avoidance of social safety in Magel2 KO mice were associated with reduced engagement of oxytocin neurons in the SON, but not the PVN. Conclusion In a preclinical model of PWS/SYS, we demonstrated region-specific deficit in oxytocin neuron activity associated with behavioral generalization of social fear to social safety. Insights from this study add to our understanding of oxytocin action in the brain at the intersection of social trauma and PWS/SYS.
RESUMO
The relation between pesticides exposure and metabolic syndrome (MetS) has not been clearly identified. Performing a systematic review and meta-analysis, PubMed, Cochrane Library, Embase, and ScienceDirect were searched for studies reporting the risk of MetS following pesticides exposure and their contaminants. We included 12 studies for a total of 6789 participants, in which 1981 (29.1%) had a MetS. Overall exposure to pesticides and their contaminants increased the risk of MetS by 30% (95CI 22%-37%). Overall organochlorine increased the risk of MetS by 23% (14-32%), as well as for most types of organochlorines: hexachlorocyclohexane increased the risk by 53% (28-78%), hexachlorobenzene by 40% (0.01-80%), dichlorodiphenyldichloroethylene by 22% (9-34%), dichlorodiphenyltrichloroethane by 28% (5-50%), oxychlordane by 24% (1-47%), and transnonchlor by 35% (19-52%). Sensitivity analyses confirmed that overall exposure to pesticides and their contaminants increased the risk by 46% (35-56%) using crude data or by 19% (10-29%) using fully-adjusted model. The risk for overall pesticides and types of pesticides was also significant with crude data but only for hexachlorocyclohexane (36% risk increase, 17-55%) and transnonchlor (25% risk increase, 3-48%) with fully-adjusted models. Metaregressions demonstrated that hexachlorocyclohexane increased the risk of MetS in comparison to most other pesticides. The risk increased for more recent periods (Coefficient = 0.28, 95CI 0.20 to 0.37, by year). We demonstrated an inverse relationship with body mass index and male gender. In conclusion, pesticides exposure is a major risk factor for MetS. Besides organochlorine exposure, data are lacking for other types of pesticides. The risk increased with time, reflecting a probable increase of the use of pesticides worldwide. The inverse relationship with body mass index may signify a stockage of pesticides and contaminants in fat tissue.