Effect of melatonin on blood-brain barrier disruption in the hippocampus of type 1 diabetic rats

Diabetes mellitus is characterized by hyperglycemia due to lack of insulin production or function. Chronic hyperglycemia leads to damage microvascular dysfunction, including in hippocampus. Previous studies found that diabetes can cause blood-brain barrier (BBB) dysfunction and implicate cognitive decline in the hippocampus. BBB comprises endothelial cells attached with tight junctions to protect pathogens in circulation through the brain parenchyma. Interestingly, melatonin, a neurohormone secreted from pineal gland, is a neuroprotective effect and plays a vital role in learning and memory. This study aims to examine protective effect of melatonin on blood-brain barrier dysfunction that leads to cognitive impairment. Rats were randomly divided into control, diabetes, melatonin-treated diabetes, and melatonin groups. In diabetic group, rats were induced by streptozotocin via intraperitoneal injection at single dose of 60 mg/kg. Afterward, the rats received 10 mg/kg of melatonin via intraperitoneal injection or vehicle for eight weeks. Morris water maze test was evaluated for cognitive function in the seventh week, and hippocampus was collected. Co-localization of endothelial cells (CD31) and tight junction protein (claudin-5 and ZO-1) was determined to blood-brain barrier function by immunohistochemistry. The results of MWM revealed that diabetic group spent less time in target quadrant compared to control group. However, melatonin-treated diabetic rats spent more time in target quadrant. Moreover, the expression of claudin-5 and ZO-1 in diabetic group significantly decreased compared to control group. Melatonin administration upregulated tight junction protein expressions. Our finding indicates that melatonin can protect against diabetes-associated blood-brain barrier injury and promote cognitive function in the hippocampus.