Melatonin reverses cognitive deficits in streptozotocin-induced type 1 diabetes in the rat through attenuation of oxidative stress and inflammation

Ala Albazal | Alireza Azizzadeh Delshad | Mehrdad Roghani

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URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=148279
Date :  2021/03/01
Publish in :    Journal of Chemical Neuroanatomy
DOI :  https://doi.org/10.1016/j.jchemneu.2020.101902
Link :  http://dx.doi.org/10.1016/j.jchemneu.2020.101902
Keywords :Diabetes mellitus, Streptozotocin, Melatonin, Cognition, Learning and memory

Abstract :

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Uncontrolled diabetes mellitus (DM) is linked to attentional deficits and cognition deterioration. The neurohormone melatonin is an endogenous synchronizer of circadian rhythms with multiple protective properties. This research was designed to assess its effect against learning and memory decline in streptozotocin (STZ)-induced diabetic rats. Rats were assigned to control, melatonin-treated control, diabetic, and melatonin-treated diabetic groups. Melatonin was administered i.p. at a dose of 10 mg/kg/day for 47 days. Treatment of diabetic rats with melatonin reversed decline of spatial recognition memory in Y maze, performance of rats in novel object discrimination, and retention and recall in passive avoidance tasks. Furthermore, melatonin appropriately attenuated hippocampal malondialdehyde (MDA) and reactive oxygen species (ROS) and improved superoxide dismutase (SOD) activity and improved mitochondrial membrane potential (MMP) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with no significant effect on nitrite, glutathione (GSH) and catalase activity. Besides, hippocampal level of acetylcholinesterase (AChE), glial fibrillary acidic protein (GFAP), nuclear factor-kappaB (NF-κB), interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) decreased following melatonin treatment. There was also a reduction of dendritic spines of pyramidal neurons of hippocampal CA1 area in diabetic group that was significantly alleviated upon melatonin treatment. Melatonin could ameliorate learning and memory disturbances in diabetic rats through mitigation of cholinesterase activity, astrocytes, oxidative stress and inflammation and also via upregulation of some antioxidants in addition to its prevention of dendritic spine loss