Rats Exposed to Prenatal Stress Are Predisposed to Metabolic Syndrome and Ageing: a Signal Transduction and Treatment Study.

Rationale: Prenatal synthetic glucocorticoids are administered to pregnant women at risk of delivering preterm to advance fetal maturation and reduce neonatal morbidity and mortality, approximately 10% of all pregnancies. In humans, early-life adversity is associated with a preterm birth and a low birth weight, and can prime the neonate for further complications such as metabolic syndrome later in life. In rat, offspring from the stressed dams were more susceptible to metabolic syndrome when fed on a high-fat diet and that this susceptibility was due to excessive exposure of the developing fetus to maternal glucocorticoid. Metabolic syndrome refers to the clustering of various metabolic risk factors that include obesity, dyslipidemia, hypertension, and hyperglycemia. Metabolic syndrome and its comorbidities have been increasing worldwide and are becoming a heavy burden to both healthcare costs and mortality. Metabolic syndrome is now considered diseases of developmental origin. Moreover, accumulating evidence implies that metabolic syndrome contributes to the development and progression of Alzheimer’s disease and ageing process. Metabolic syndrome is linked with insulin resistance in multiple organs, endothelium dysfunction and cardiovascular dysfunction, and systemic inflammation. Metabolic syndrome may have long-term impacts on multiple peripheral organs including liver, pancreas, and adipose tissue and brain, specifically, the hippocampus and causing mental disorders and learning and memory. In order to address these issues, our aims are as follows: 1. To study the cross talk among insulin, insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in both ventral and dorsal hippocampus in 6-month old rat with prenatal stress and postnatal high-fat diet (1st yr). 2. To study the programming effect outside the brain, including plasma, liver, pancreas, and adipose tissue in terms of insulin, IGF-1, TNF-α, and ADMA signaling (2nd yr). 3. To study the cross talk among insulin, IGF-1, TNF-α, and ADMA in prenatal stress age offspring hippocampus and examine the possible therapeutic effect of melatonin (3rd yr).

Project ID:PC10508-0356
External Project ID:MOST105-2314-B182-055