Peripubertal treatment of Lewis dwarf rats with GH results in a significant extension of life span. The present study was designed to test the role of the GH/IGF-1 axis in regulating cellular

oxidative stress and oxidative stress resistance, utilizing primary fibroblasts derived from control rats. Lewis dwarf rats and GH-replete dwarf rats. Measurements of cellular dihydroethidium and C-H(2)-DCFDA fluorescence showed that cellular O(2)(center dot-) and peroxide production were similar in each group. Fibroblasts from control and Lewis dwarf rats exhibited similar antioxidant capacities and comparable sensitivity to H(2)O(2), IGF-1R inhibitor rotenone, high glucose, tunicamycin, thapsigargin, paraquat, and mitomycin, which cause apoptosis through increasing oxidative stress, mitochondrial damage. ATP depletion, and/or by damaging DNA, lipids and proteins. Fibroblasts from GH-replete rats exhibited significantly increased antioxidant capacities and superior resistance to H(2)O(2), rotenone and bacterial lipopolysaccharide-induced cell death compared with cells from selleck compound Lewis dwarf rats, whereas their sensitivity to the other stressors investigated was not

statistically different. Thus, low circulating IGF-1 levels present in vivo in Lewis dwarf rats do not elicit long-lasting alterations in cellular reactive oxygen species generation and oxidative stress resistance, whereas life span-extending peripubertal GH treatment resulted in increased antioxidant capacity and increased resistance to cellular injury caused by some, but not all, oxidative stressors.”
“Ketamine, an NMDA-receptor antagonist, produces cognitive deficits in humans in a battery of tasks involving attention and memory. Nicotine can enhance various indices of cognitive performance, including working memory span capacity measured using the odor span task (OST). This study examined the effects of a sub-chronic

ketamine treatment to model cognitive deficits associated with schizophrenia, and to evaluate the effectiveness of nicotine, antipsychotic clozapine, and the novel mGlu2/3 agonist, LY404039, in restoring OST performance. Male mafosfamide hooded Lister rats were trained in the OST, a working memory task involving detection of a novel odor from an increasing number of presented odors until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, administration of graded doses of nicotine (0.025-0.1 mg/kg) acutely restored the performance in ketamine-treated animals, while significant improvements in odor span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1-10 mg/kg) and LY404039 (0.