کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4342310 1295862 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
11β-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
11β-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids
چکیده انگلیسی

11β-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert 11-keto derivatives. As 11β-hydroxysteroid dehydrogenase type 2 is highly expressed in the developing brain, but not in the adult CNS, we hypothesized that it may represent a protective barrier to the deleterious actions of corticosteroids on proliferating cells. To test this hypothesis we have investigated the development and growth of the cerebellum in neonatal C57BL/6 mice and mice lacking 11β-hydroxysteroid dehydrogenase type 2 (−/−). 11β-Hydroxysteroid dehydrogenase type 2−/− mice had consistently lower body weight throughout the neonatal period, coupled with a smaller brain size although this was normalized when corrected for body weight. The cerebellar size was smaller in 11β-hydroxysteroid dehydrogenase type 2−/− mice, due to decreases in size of both the molecular and internal granule layers. When exogenous corticosterone was administered to the pups between postnatal days 4 and 13, 11β-hydroxysteroid dehydrogenase type 2−/− mice were more sensitive, showing further inhibition of cerebellar growth while the wildtype mice were not affected. Upon withdrawal of exogenous steroid, there was a rebound growth spurt so that at day 21 postnatally, the cerebellar size in 11β-hydroxysteroid ehydrogenase type 2−/− mice was similar to untreated mice of the same genotype. Furthermore, 11β-hydroxysteroid dehydrogenase type 2−/− mice had a delay in the attainment of neurodevelopmental landmarks such as negative geotaxis and eye opening. We therefore suggest that 11β-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 137, Issue 3, 2006, Pages 865–873
نویسندگان
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