Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats

Background: High-fat diet (HFD) is a detrimental habit with harmful systemic consequences, including low-grade, long-lasting inflammation. During pregnancy, HFD can induce developmental changes. Moreover, HFD-related maternal obesity might enhance the risk of peripartum complications including hypoxic-ischemic encephalopathy secondary to perinatal asphyxia (PA).

Objectives: Following our previous results showing that PA increases neuroinflammation and neuronal injury in the immature hippocampus and modifies hippocampal epigenetic programming, we further aimed to establish the impact of maternal HFD on offspring hippocampus response to PA.

Methods: We assessed hippocampal tumor necrosis factor alpha (TNFα), interleukin 1 beta -(IL-1b) and S-100B protein (S-100B), 24-48 h after PA exposure in postnatal day 6 Wistar rats, whose mothers received either the standard diet or HFD. The expression of small non-coding microRNA species miR124, miR132, miR134, miR146, and miR15a, as epigenetic markers for the maternal dietary influence on immature hippocampus response after PA, was determined 24 h after asphyxia exposure. Metabolic activity was measured using resazurin test in hippocampal cell suspension obtained 24 h after PA.

Results: Our results indicate that maternal HFD additionally increases hippocampal TNFα, IL-1b, and S-100B after PA. Also, PA associated with maternal HFD induces miR124 upregulation and miR132 downregulation relative to PA only. Metabolic activity was increased in hippocampal cells from pups whose mothers received HFD.

Conclusion: HFD increases the PA-induced neuroinflammation and neuronal injury, and epigenetically influences homeostatic synaptic plasticity and neuronal tolerance to asphyxia, processes associated with a higher hippocampal cellular metabolism.