Exogenous melatonin restrains neuroinflammation in high fat diet induced diabetic rats through attenuating indoleamine 2,3-dioxygenase 1 expression.

AIM OF THE WORK

Neuroinflammation can arise from metabolic disturbances accompanying type 2 diabetes mellitus (T2DM) with an implication of indoleamine 2,3-dioxygenase 1 (IDO1). The antioxidant and anti-inflammatory potentials of melatonin (Mel) can amend diabetic complications. Here, we examined the effect of exogenous melatonin on neuroinflammation in high fat diet (HFD)-induced T2DM rats.

MAIN METHODS

Twenty-one adult male Sprague-dawley rats were divided in to three groups: control group: fed commercial standard rat chow, T2DM group: fed with HFD for 16 weeks, and T2DM-Mel group: received HFD for 8 weeks, followed by weekly melatonin treatment (i.p injection 10 mg/kg in saline) for 8 weeks with continuous supply of HFD. After which, animals were submitted to euthanasia for brain and blood samples collection.

KEY FINDINGS

In T2DM-Mel group the diabetic profile was ameliorated, and the state of low-grade systemic inflammation was alleviated through lowering serum pro-inflammatory cytokines (TNF-α and IL-6) and leptin while increasing adiponectin. Melatonin improved brain oxidative stress by increasing total antioxidant capacity and reduced glutathione (GSH), whereas malondialdehyde was declined. Melatonin reduced acetylcholinesterase (AChE) activity in blood and brain and its hippocampal expression, also hippocampal inducible nitric oxide synthase (iNOS) expression was reduced, moreover IDO1 hippocampal expression was declined, furthermore recovered neuronal morphology following melatonin treatment was also clearly viewed in the hippocampus under the light microscope in T2DM-Mel rats.

SIGNIFICANCE

Melatonin can be considered as a promising solution in preventing neuroinflammation development in T2DM owing to its ability to render the oxidative stress and accompanied low-grade systemic inflammation.