Role of the nitric oxide-soluble guanylyl cyclase pathway in cognitive deficits in streptozotocin-induced diabetic rats
| Autor: | Tijen Utkan, Feyza Aricioglu, Yusufhan Yazir, Selen Polat |
|---|---|
| Přispěvatelé: | Yazir, Yusufhan, Polat, Selen, Utkan, Tijen, Aricioglu, Feyza |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Morris water navigation task Neurosciences. Biological psychiatry. Neuropsychiatry passive avoidance YC-1 Cyclase Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Diabetes mellitus zaprinast PHOSPHODIESTERASE-5 INHIBITOR Internal medicine Guanosine monophosphate medicine Pharmacology (medical) MESSENGER-RNA EXPRESSION BRAIN DEPENDENT PROTEIN-KINASE IN-VIVO MEMORY MOUSE MODEL Streptozotocin medicine.disease CGMP LEVELS SILDENAFIL Psychiatry and Mental health 030104 developmental biology Endocrinology chemistry LONG-TERM POTENTIATION Zaprinast Soluble guanylyl cyclase Morris water maze 030217 neurology & neurosurgery RC321-571 medicine.drug dementia |
| Zdroj: | Psychiatry and Clinical Psychopharmacology, Vol 29, Iss 1, Pp 34-44 (2019) |
| Popis: | OBJECTIVES: The impairment of cognitive functions in diabetes mellitus (DM) is well known. Nitric oxide (NO)-guanyly cyclase (GC)-cyclic guanosine monophosphate (cGMP) pathway is an important role in cognitive functions, and, consequently, phosphodiesterase-5 (PDE-5) inhibitors as well as NO-GC activators are of considerable interest in the treatment of cognitive deficits. Therefore, we aimed to investigate the effects of YC-1 (3-5-hydroxymethyl-2-furyl)-1-benzyl-indazole), an NO-GC activator, and zaprinast, a PDE-5 inhibitor, on cognitive dysfunction in streptozotocin (STZ)-induced diabetic rats. METHODS: Male Wistar rats were divided into five groups (nine rats in each): Control, Vehicle (DMSO), Diabetic (50 mg/kg/i.p. streptozotocin), Diabetic-YC-1 (1 mg/kg/day/i.p., for 4 weeks), and Diabetic-Zaprinast (10 mg/kg/day/i.p., for 4 weeks) group. The Morris water maze, passive avoidance, locomotor activity, and foot shock sensitivity tests were applied to assess the effect of YC-1 and zaprinast on learning and memory. To explore the mechanisms of YC-1 and zaprinast on learning and memory performance, protein expressions of brain-derived neurotrophic factor (BDNF) in hippocampus were examined immunohistochemically. RESULTS: Thirty days after the induction of DM, rats exhibited severe learning and memory dysfunctions associated with decreased BDNF expression. Both chronic YC-1 and zaprinast treatment improved cognitive performance and hippocampal BDNF expression in diabetic rats. In the locomotor activity and foot shock sensitivity test, no significant differences were observed between the groups. Furthermore, hyperglycaemia did not affect cognition enhancement effects of YC-1 or zaprinast in diabetic rats. CONCLUSIONS: Our findings highlight the beneficial effects of nitric oxide-guanylyl cyclase activators and PDE-5 inhibitors to improve cognitive function in diabetes. |
| Databáze: | OpenAIRE |
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