Molecular and biochemical mechanisms in streptozotocin-induced diabetes and associated behavioral indices

• Κύριος συγγραφέας: Κοκκόσης, Αλέξανδρος
• Άλλοι συγγραφείς: Μαργαρίτη, Μαριγούλα
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2015
• Θέματα: Type I diabetes; Cognitive dysfunction; Cholinergic system; Oxidative stress; Neuronal apoptosis; Brain regions; Διαβήτης τύπου Ι; Γνωστικές δυσλειτουργίες; Χολινεργικό σύστημα; Οξειδωτικό στρές; Νευρωνική απόπτωση; Εγκεφαλικές περιοχές; 616.462 206 107 24

Diabetic encephalopathy, characterized by impaired cognitive function may involve neuronal dysfunction and neurochemical abnormalities. Here we investigated the effects of streptozotocin-induced type I diabetes (T1D) and its treatment by insulin on behavioral indices and the neurochemical profile in male mice. We focused on the cholinergic system and brain oxidative profile. Mice (n=32) were divided into three groups (n=10-11/group). Two groups became diabetic by intraperitoneal administration of streptozotocin (50mg/kg body weight/per day), for five consecutive days. After 21 days one diabetic group was treated intraperitoneally with glargine (6 IU/kg) for an additional six days. As control, the third group of the study remained euglycemic. All three groups underwent behavioral analysis (fear-anxiety, memory-learning and depression-like behavior) two days following insulin administration to diabetic mice. Also, plasma glucose, cholesterol and triglycerides levels, were determined. In addition, biochemical analyses including determination of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activity, as well the activities of superoxide dismutase, glutathione peroxidase, catalase, glutathione levels (markers of antioxidant defense), and malondialdehyde (marker of lipid peroxidation),were performed in various brain regions (cerebral cortex, midbrain, hippocampus, striatum, diencephalon and cerebellum). Our data indicate that T1D engendered anxiogenesis, memory loss and depression-like behavior in mice that were associated with statistically significant decrease in ACh levels and a parallel increase in the AChE activity in the brain regions studied. The enzymatic anti-oxidant activity was significantly increased in diabetic mice presumably as a means of defense against the increased oxidative stress. Western blot analysis on mitochondrial lysates and cytoplasmic samples indicated neuronal apoptosis on most of the brain regions examined (cerebellum, cerebral cortex, midbrain, hippocampus, striatum and diencephalon). Insulin treatment significantly attenuated the cognitive deficits, cholinergic dysfunction, oxidative stress and neuronal apoptosis the diabetic mice in a brain region-dependent manner. Our findings support that T1D leads to cognitive dysfunction, cholinergic system aberrations, oxidative stress and neuronal apoptosis, which are reversed following insulin treatment.