Excessive fructose consumption induces metabolic syndrome (MetS) characterised by hyperglycaemia, dyslipidaemia, obesity and a decline in cognitive capacity, partly due to derangements in the hippocampus. We evaluated the potential protective effects of neonatally administering oleanolic acid (OA) against high fructose-induced reduction in granule cell layer volume, cell density and neurogenesis in the rat dentate gyrus (DG). Sprague Dawley rat pups (seven days old) were randomly assigned to three groups and administered orally: distilled water (DW), high fructose diet (20%w/v) and oleanolic acid (OA; 60 mg/kg) for 7 days. The rats were weaned (21 days old) onto normal rat chow diets up to post-natal day 55. From post-natal day 56-110, half of the rats in each experimental group were continued on plain water while the other half on a high fructose solution to drink. The rats were euthanized on day 112, before blood, visceral fat and brain tissue samples were collected. Body adiposity and impact on lipid metabolism was determined by measuring plasma triglycerides and visceral fat accumulation while brain tissue was used for histology. High fructose (HF) consumption led to the development of body adiposity (increased visceral fat accumulation), dyslipidaemia (increased triglyceride levels) and apoptosis in the DG. In addition, HF led to significant (p<0.05) reductions in volume, cell density and neurogenic activity in the dentate gyrus of the hippocampus. However, administration of OA during the neonatal period attenuated these deleterious effects of high fructose. We conclude that orally administered OA in the neonatal period may potentially be used to prevent the development of fructose-induced deleterious effects on the brain and most likely cognitive function. National Research Foundation of South Africa (grant number IRF 2010041900009). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.