title: Davunetide (NAP) as a preventative treatment for central nervous system complications in a diabetes rat model.
abstract: OBJECTIVE
  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.
authors.affiliation: The Adams Super Center for Brain Studies, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Idan-Feldman
authors.forename: Yulie
authors.initials: Y
authors.lastname: Schirer
authors.forename: Eleni
authors.initials: E
authors.lastname: Polyzoidou
authors.forename: Olga
authors.initials: O
authors.lastname: Touloumi
authors.forename: Roza
authors.initials: R
authors.lastname: Lagoudaki
authors.forename: Nikolaos C
authors.initials: NC
authors.lastname: Grigoriadis
authors.forename: Illana
authors.initials: I
authors.lastname: Gozes
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D037102:Lectins / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D001523:Mental Disorders / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012919:Social Behavior; D013028:Space Perception / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D037102:Lectins; D018696:Neuroprotective Agents; D009842:Oligopeptides; D016708:Synaptophysin; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; C425904:davunetide