Abstract
Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1–3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials.
Highlights
Diabetes mellitus (DM) is a disorder in which abnormalities in carbohydrate, fat, and protein metabolisms develop due to the deficiency or dysfunction of the insulin hormone [1]
Cardiovascular, cerebrovascular, and peripheral vascular diseases as well as retinopathy, neuropathy, and nephropathy can be listed as the major chronic complications of DM [2]
The effect of agomelatine treatment on chronic hyperglycemia-induced neurobehavioral alterations was investigated in an experimental model of diabetes, which was established by streptozotocin (STZ, a N-nitroso derivative of glucosamine)
Summary
Diabetes mellitus (DM) is a disorder in which abnormalities in carbohydrate, fat, and protein metabolisms develop due to the deficiency or dysfunction of the insulin hormone [1]. Having a high prevalence in the worldwide, DM has a special clinical importance in terms of the complications it causes. Acute complications of DM, which are caused by absolute or relative deficiency of insulin, are diabetic ketoacidosis, hyperosmolar non-ketotic syndrome, and comas induced by lactic acidosis or hypoglycaemia [2]. DM can lead to chronic complications that are characterized by impaired and insufficient functions of the various systems, organs, and tissues due to the long-term metabolic disturbances. Harmful effects of DM on the central nervous system (CNS), entitled as diabetic encephalopathy [3], is classified as a chronic complication of DM [4]
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