title: Pyridoindole antioxidant-induced preservation of rat hippocampal pyramidal cell number linked with reduction of oxidative stress yet without influence on cognitive deterioration in Alzheimer-like neurodegeneration.
abstract: BACKGROUND
  The idea of antioxidant therapy attenuating Alzheimer disease (AD) neuropathology starts to be attractive. Animal models are often used in these studies. An AD-like model of trimethyltin (TMT)-induced neurodegeneration, targeting the hippocampus, involves neuronal cell death and cognitive impairment.
  
  
  OBJECTIVE
  Effect of the pyridoindole SMe1EC2 (3×50 mg/kg) and vitamin C (3×50mg/kg) was analyzed in the model of TMT-induced (8 mg/kg) neurodegeneration.
  
  
  METHODS
  The study was focused on the effect of the antioxidants tested on learning performance in the Morris water maze (MWM) on days 21-25 after TMT administration, on biochemical variables - malondyaldehyde (MDA) and lysosomal enzyme NAGA in brain cortex and blood serum, and on pyramidal cell number in the CA1 area of the hippocampus on day 31 after TMT administration in adult male Wistar rats (n=32).
  
  
  RESULTS
  Critical deterioration of learning performance was observed due to the TMT administration in the MWM. Further, apparent reduction of pyramidal cell number to 21% in the CA1 area of the hippocampus, increased MDA and NAGA activity in serum and increased NAGA activity in the cortex were determined contrary to controls. In serum, an increase of MDA level was prevented by both antioxidants tested without any effect on NAGA activity. SMe1EC2 apparently preserved pyramidal cell viability in the CA1 area. Both substances tested failed to ameliorate the detrimental effect of TMT on spatial memory.
  
  
  CONCLUSIONS
  The biochemical and morphometrical findings suggest that reduction of oxidative stress may play a role in AD-like neurodegeneration. Different doses and timing of SMe1EC2 administration might bring improvement in next learning performance.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Gasparova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Stara
authors.affiliation: Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Pavol
authors.initials: P
authors.lastname: Janega
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Jana
authors.initials: J
authors.lastname: Navarova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sedlackova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Mojmir
authors.initials: M
authors.lastname: Mach
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ujhazy
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D007211:Indoles; D018696:Neuroprotective Agents; D011725:Pyridines; C534359:SMe1EC2; D008315:Malondialdehyde; D000118:Acetylglucosaminidase