Gestational Diabetes Mellitus Triggers Maternal Premature Brain Aging and Brain Pathologies
Huatuo Huang, Thura Tun Oo, Nattayaporn Apaijai, Panan Suntornsaratoon, Narattaphol Charoenphandhu, Nipon Chattipakorn, Siriporn C Chattipakorn- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
It has been well‐documented that diabetes mellitus (DM) causes brain pathologies and premature brain aging. Previous studies showed that women with gestational diabetes mellitus (GDM) are at a high risk to develop depression. It is unclear whether GDM can lead to brain pathologies and premature brain aging, thus contributing to cognitive behavior changes as observed in human and animal studies.
Method
Female Sprague‐Dawley rats were fed either a normal diet (ND, 5% kcal from fat) or a high‐fat diet (HFD, 45% kcal from fat) throughout the entire study. At week 4, rats were mated overnight with ND‐fed male rats, and successful pregnancy was denoted as pregnancy day 0 (P0). At P0, HFD‐treated rats were intraperitoneally injected with a single‐dose streptozotocin (STZ, 35 mg/kg) to induce DM or the same amount of vehicle as HFD‐control. The ND‐treated rats received the same amount of vehicle as the ND‐control. Oral glucose tolerance test and plasma insulin levels were assessed at pregnancy day 16 to confirm the GDM model. At postpartum day 21, maternal rats were sacrificed, and brains were rapidly removed to determine brain pathologies and premature brain aging in the prefrontal cortex and hippocampus.
Result
Rats treated with HFD and HFD+STZ developed prediabetes and diabetes conditions, respectively. GDM induced brain inflammation and brain cell senescence, as indicated by increases in nuclear factor kappa‐light‐chain‐enhancer of activated B, senescence‐associated beta‐galactosidase, and p16 expression in the prefrontal cortex and hippocampus (Figure 1). Furthermore, mitochondrial fusion was enhanced, while brain apoptosis was attenuated in the prefrontal cortex and hippocampus of GDM rats (Figure 1).
Conclusion
GDM triggers maternal brain pathologies as well as premature brain aging in both prefrontal cortex and hippocampus. Our findings highlight that the brain may have compensatory mechanisms that can help guard against the negative effects of GDM.