Improved perinatal glucose metabolism and the effect on the offspring's hippocampus in the mouse

• Applicants: Dr. Sarah Appel; Dr. Eva Hucklenbruch-Rother
• Subject Area: Gynaecology and Obstetrics
• Term: from 2014 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256548693

Maternal obesity before and during pregnancy is becoming more common in the face of a steadily increasing global prevalence of overweight and obesity. Unfortunately, there are many risks to both, the mother and the child. In addition to the predisposition of the child for cardiovascular and metabolic diseases, such as arterial hypertension, type 2 diabetes or obesity, maternal periconceptual obesity also causes an increased occurrence of neurocognitive developmental disorders and mental illnesses. Based on preliminary work in the animal model we were able to show that maternal obesity leads to a disturbed glucose metabolism around birth and during the first weeks of life of the offspring. In adulthood, the offspring’s hippocampus shows resistance to insulin and altered neuronal plasticity. The functional consequences of these hippocampal changes have not yet been investigated. Furthermore, it is unclear whether an improvement in perinatal glucose metabolism has the potential to prevent hippocampal insulin resistance and altered neuronal plasticity. Both questions will be addressed in the requested project. The offspring of normal-weight and overweight dams will be tested with regard to anxiety, learning, social and depressive behaviour at postnatal days 56 (adolescence) and molecular processes in the hippocampus (insulin sensitivity, markers of neuronal plasticity and proteomic screening analysis) will be investigated in parallel. In addition, it will be tested whether two well-established measures to improve perinatal glucose metabolism (maternal running-wheel training or treatment with the insulin sensitizer metformin during pregnancy) are able to reduce the consequences of maternal obesity in the offspring's hippocampus and behaviour. Finally, the findings of the animal experiments will be used to develop a specific strategy for the investigation of a human mother-child cohort that is accessible via a collaborator. In summary, the project aims at a better understanding of the neurocognitive and behavioural consequences of maternal obesity for the offspring and will help to develop prevention and treatment strategies.

• DFG Programme: Research Grants