کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6258107 1612964 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research reportProtective effects of phosphodiesterase 2 inhibitor on depression- and anxiety-like behaviors: Involvement of antioxidant and anti-apoptotic mechanisms
ترجمه فارسی عنوان
گزارش تحقیقات اثرات محافظتی مهار کننده فسفودی استراز 2 بر رفتارهای افسردگی و اضطراب: درگیر شدن از مکانیسم های آنتی اکسیدانی و ضد آپوپتوز
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
چکیده انگلیسی


- Bay 60-7550 exhibits antidepressant- and anxiolytic-like effects in mouse behaviors.
- Increased cGMP signaling may contribute to the protective effects of Bay 60-7550.
- Bay 60-7550 is able to antagonize the oxidative damage produced by chronic stress.
- Another possible mechanism of Bay 60-7550's function is its anti-apoptotic effects.

Stress occurs in everyday life, but the relationship between stress and the onset or development of depression/anxiety remains unknown. Increasing evidence suggests that the impairment of antioxidant defense and the neuronal cell death are important in the process of emotional disorders. Chronic stress impairs the homeostasis of antioxidants/oxidation, which results in the aberrant stimulation of the cell cycle proteins where cGMP-PKG signaling is thought to have an inhibitory role. Phosphodiesterase 2 (PDE2) is linked to cGMP-PKG signaling and highly expressed in the limbic brain regions including hippocampus and amygdala, which may play important roles in the treatment of depression and anxiety. To address the possible effects of PDE2 inhibitors on depression-/anxiety-like behaviors and the underlying mechanisms, Bay 60-7550 (0.75, 1.5 and 3 mg/kg, i.p.) was administered 30 min before chronic stress. The results suggested that Bay 60-7550 not only restored the behavioral changes but also regulated Cu/Zn superoxide dismutase (SOD) levels differentially in hippocampus and amygdala, which were increased in the hippocampus while decreased in the amygdala. It was also significant that Bay 60-7550 regulated the abnormalities of pro- and anti-apoptotic components, such as Bax, Caspase 3 and Bcl-2, and the indicator of PKG signaling characterized by pVASPser239, in these two brain regions. The results suggested that Bay 60-7550 is able to alleviate oxidative stress and mediate part of the apoptotic machinery in neuronal cells possibly through SOD-cGMP/PKG-anti-apoptosis signaling and that inhibition of PDE2 may represent a novel therapeutic target for psychiatric disorders, such as depression and anxiety.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 268, 15 July 2014, Pages 150-158
نویسندگان
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