title: Androgen treatment of neonatal rats decreases susceptibility of cerebellar granule neurons to oxidative stress in vitro.
abstract: Oxidative stress has been implicated in various neurodegenerative diseases. There is substantial evidence indicating that gonadal hormones can affect neuronal cell survival via both a genomic as well as a non-genomic mode of action. In the present study, the potential protective activity of testosterone on neuronal cells was investigated by using an in vitro/ex vivo model. Cerebellar granule cells (CGC) were prepared from 7-day-old rats which had been treated with a single dose of oil or testosterone propionate on postnatal day 3. After 7 days in culture, cells were exposed to oxidative challenges, including hydrogen peroxide and the nitric oxide donor S-nitrosocysteine (SNOC), which can induce CGC death via apoptosis. Colchicine, which causes apoptosis via a different mechanism, was also used. The cells were monitored for apoptotic morphology by propidium iodide and TUNEL staining. Additionally, the presence of chromatin fragmentation was determined. CGC obtained from testosterone-treated rats were found to be more resistant to hydrogen peroxide and nitric oxide toxicity, as shown by a 75 and 45% decrease in apoptotic cells, respectively. In contrast, the susceptibility to colchicine was not modified. As CGC from testosterone-treated pups were selectively protected from oxidative stress, different components of the antioxidant defence systems were analysed. A twofold increase in the activity of catalase and superoxide dismutase was found in the CGC prepared from testosterone-treated rats. These results suggest that in vivo treatment with androgens render CGC less vulnerable to oxidative stress-induced apoptosis by potentiating antioxidant defences.
authors: Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors: E
authors: E
authors: Ahlbom
authors: L
authors: L
authors: Grandison
authors: E
authors: E
authors: Bonfoco
authors: B
authors: B
authors: Zhivotovsky
authors: S
authors: S
authors: Ceccatelli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D003078:Colchicine / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D053938:DNA Fragmentation; D004198:Disease Susceptibility; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013739:Testosterone; C021315:S-nitrosocysteine; D006861:Hydrogen Peroxide; D003545:Cysteine; D003078:Colchicine