کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5829704 1558999 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metyrapone effects on systemic and cerebral energy metabolism
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Metyrapone effects on systemic and cerebral energy metabolism
چکیده انگلیسی
Metyrapone is a cytochrome P450 inhibitor that protects against ischemia- and excitotoxicity-induced brain damages in rodents. This study examines whether metyrapone would act on energy metabolism in a manner congruent with its neuroprotective effect. In a first investigation, the rats instrumented with telemetric devices measuring abdominal temperature, received i.p. injection of either metyrapone or saline. One hour after injection, their blood and hippocampus were sampled. Hippocampus metabolite concentrations were measured using 1H high-resolution magic angle spinning-magnetic resonance spectroscopy (1H HRMAS-MRS). The hippocampus levels in phosphorylated mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) were measured by Western Blot analysis and those of c-fos and HSP70-2 mRNA were quantified by RT-PCR. In a second investigation, the rats received the same treatment and were sacrificed 1 h after. The functioning of mitochondria was immediately studied on their whole brain. Metyrapone provoked a slight hypothermia which was correlated to the increase in blood glucose concentration. Metyrapone also increased blood lactate concentrations without modifying hippocampus lactate content. In the hippocampus, metyrapone decreased γ-aminobutyric acid (GABA) and glutamate levels but increased glutamine and N-acetyl-aspartate contents (NAA). Phosphorylated mTOR and AMPK and the c-fos and HSP70-2 mRNA levels were similar between treatment groups. Metyrapone did not modify blood corticosterone levels. Mitochondrial oxygen consumption was similar in both groups whatever the substrate used. These metabolic modifications, which take place without modifying blood glucocorticoid levels, are consistent with the neuroprotective properties of metyrapone as demonstrated in animal models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 682, Issues 1–3, 5 May 2012, Pages 92-98
نویسندگان
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