Davunetide (NAP) as a preventative treatment for central nervous system complications in a diabetes rat model
| Autor: | Eleni Polyzoidou, Olga Touloumi, Illana Gozes, Roza Lagoudaki, Nikolaos Grigoriadis, Anat Idan-Feldman, Yulie Schirer |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Central nervous system Synaptophysin Morris water navigation task Hippocampus Water maze Diabetes Mellitus Experimental lcsh:RC321-571 Rats Sprague-Dawley Cognition Diabetes complications Central Nervous System Diseases Internal medicine Diabetes mellitus Lectins Reaction Time Medicine Animals Prefrontal cortex Maze Learning Social Behavior lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry business.industry Caspase 3 Streptozotocin Mental Disorders medicine.disease NAP (davunetide) Magnetic Resonance Imaging Immunohistochemistry Rats Nap Disease Models Animal medicine.anatomical_structure Endocrinology Neuroprotective Agents Neurology Phosphopyruvate Hydratase Space Perception business Cognition Disorders Oligopeptides medicine.drug MRI |
| Zdroj: | Neurobiology of Disease, Vol 44, Iss 3, Pp 327-339 (2011) |
| Popis: | Aims Central nervous system complications including cognitive impairment are an early manifestation of diabetes mellitus, also evident in animal models. NAP (generic name, davunetide), a neuroprotective peptide was tested here for its ability to prevent diabetes-related brain pathologies in the streptozotocin injected diabetes rat model. Methods Diabetes was induced by an intraperitoneal streptozotocin injection (55 mg/kg). Intranasal NAP or vehicle was administered daily starting on the day following streptozotocin injection. Cognitive assessment was performed 12 weeks after diabetes induction, using the Morris water maze paradigm. Brain structural integrity was assessed on the 15th week of diabetes by magnetic resonance T2 scan. Characterization of cellular populations, apoptosis and synaptic density was performed 16 weeks after diabetes induction, using immunohistochemical markers and quantified in the prefrontal cortex, the cerebral cortex and the hippocampus of both hemispheres. Results Impaired spatial memory of the diabetic rats was observed in the water maze by attenuated learning curve and worsened performance in the probe memory test. NAP treatment significantly improved both measurements. T2 magnetic resonance imaging revealed atrophy in the prefrontal cortex of the diabetes rat group, which was prevented by NAP treatment. Immunohistochemical analysis showed that NAP treatment protected against major loss of the synaptic marker synaptophysin and astrocytic apoptosis, resulting from streptozotocin treatment. Conclusions Our results show for the first time protective effects for NAP (davuentide) in a diabetes rat model at the behavioral and structural levels against one of the most severe complications of diabetes. |
| Databáze: | OpenAIRE |
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