title: Early and late stage of neurodegeneration induced by trimethyltin in hippocampus and cortex of male Wistar rats.
abstract: BACKGROUND
  Trimethyltin (TMT), a potent neurotoxicant, elicits neuronal death in the limbic system and causes damage particularly in the hippocampus. Current interest relates to the opportunity to use TMT as an experimental model of neurodegeneration in the study of Alzheimer-like diseases.
  
  
  OBJECTIVE
  In light of recently found species-specific and strain-specific differences in TMT intoxication, the aim of this study was to characterise the model of TMT-induced neurodegeneration in the brain of Wistar rats during early (days 1-3) and late (days 22-24) stage of neuronal damage.
  
  
  RESULTS
  Reduced neurotransmission at the CA3-CA1 synapse and reduced number of cells accompanied with reduced width of CA1 pyramidal cell layer were observed at the late stage of TMT intoxication (7 mg/kg, i.p.). Long-term potentiation of excitatory postsynaptic potential, elicited by train stimulation (100 Hz, 1s), was not impaired by the dose of TMT tested. Activation of pro-apoptotic caspase-3 suggests involvement of apoptosis in neuronal cell death in the hippocampus at the late stage of TMT intoxication. Increased protein carbonyl formation was proved in the cortex at the early stage of TMT intoxication compared both to controls in the early and late stage and to the late stage of TMT action.
  
  
  CONCLUSIONS
  TMT-induced neurodegeneration was proved in the brain of Wistar rats. Changes found in the parameters examined may be reliable indicators of neurodegeneration. The increased level of carbonyls in the cortex at the early stage indicates that particularly at the onset of progressive neurodegeneration compounds with antioxidative properties may be effective in slowing down brain injury.
authors: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors: Zdenka
authors: Z
authors: Gasparova
authors: Pavol
authors: P
authors: Janega
authors: Veronika
authors: V
authors: Stara
authors: Eduard
authors: E
authors: Ujhazy
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D009498:Neurotoxins; D014298:Trimethyltin Compounds; C046488:trimethyltin