Maternal consumption of a high-fat diet from pre-pregnancy to lactation impairs cognitive processes and inhibitory synaptic transmission of hippocampal neurons in mouse offspring

Maternal obesity during pregnancy is a significant global health concern, impacting the metabolic, cardiovascular, and neurological health of the offspring, the latter being a research topic that has become of great interest. Our study investigates their effects on cognition, focusing on the hippocampus, a region vulnerable to prenatal insults. While maternal high-fat diet (mHFD) has been linked to cognitive deficits and hippocampal changes, its impact on synaptic transmission remains unexplored.Our focus was to understand how this adverse prenatal environment influences memory processes and whether this is related to changes in hippocampal synaptic transmission. Using an mHFD model in mice, we exposed females from pre-pregnancy to lactation to a diet with 60% of calories from fat. Offspring underwent novel object recognition (NOR) and object localization memory (OLM) tests for cognitive assessment. Electrophysiological recordings were conducted on hippocampal CA1 region and pyramidal neurons to investigate plasticity processes and synaptic activity.The results demonstrate impaired cognitive performance in mHFD-exposed offspring, as evidenced by the reduction of discrimination indices in NOR and OLM tests. Additionally, we observed impaired long-term potentiation (LTP) and increased inhibitory synaptic efficacy in the hippocampus, indicating an excitatory/inhibitory imbalance potentially affecting cognitive function.These findings highlight synaptic alterations as potential contributors to cognitive deficits in the offspring of obese mothers, shedding light on mechanisms underlying maternal obesity-associated cognitive disorders. Addressing these alterations could offer insights into therapeutic interventions for affected individuals.