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Pre- and peri-reproduction challenges as risk factors for neurodevelopmental disorders

Applicant Dr. Ravit Hadar
Subject Area Biological Psychiatry
Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2018 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 409305455
 
Final Report Year 2023

Final Report Abstract

Maternal infection resulting in maternal immune activation (MIA) has been repeatedly identified in human epidemiologic and retrospective studies as an environmental risk factor for neurodevelopmental disorders (NDs) in the progeny. Whereas clearly MIA results in detrimental consequences in the offspring, it might also increase the susceptibility to NDs when combined with other maternal assaults, as demonstrated by retrospective human data. One such maternal assault is maternal stress in adolescence (prior to reproduction) due to enhanced alcohol consumption that could propagate to the following generations in an unfavorable manner, affecting brain and behavior. On this background, this project investigated the effects of pre- and peri-reproduction challenges in the form of adolescence alcohol exposure and maternal immune activation (MIA). The study investigated whether binge-like alcohol consumption during adolescence (prior to reproduction) with or without MIA affect the neurodevelopmental course of future generations. The study also aimed to delineate the temporal manifestation of neurodevelopmental adversities stemming from maternal alcohol consumption with and without MIA. All behavioral and neurobiological investigations in the progeny were carried out in female and male animals to address possible sex-differences. Finally, the study sought to identify biomarkers of specific endo-phenotypes. This study found that maternal pre reproduction assault in the form of adolescence alcohol consumption resulted on altered behavior, neuroanatomical changes as well as abnormal stress axis in the progeny. Neuroanatomical and stress axis abnormalities are sex-dependent. Further, the study revealed that maternal immune activation during pregnancy affects gut permeability and microbiome of the progeny.

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