کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3037227 1184406 2012 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Systemic hypoxia differentially affects neurogenesis during early mouse brain maturation
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب تکاملی
پیش نمایش صفحه اول مقاله
Systemic hypoxia differentially affects neurogenesis during early mouse brain maturation
چکیده انگلیسی

Background: Cerebral tissue oxygen level modifies crucial processes of neurogenesis, glial and neuronal development during physiological and hypoxic conditions. Whether hypoxia-sensitive factors such as doublecortin (DCX) and hypoxia-inducible transcription factor (HIF)-regulated CXCR4 and SDF-1 modify and activate adaptation to hypoxia in developing brain is not well understood. Present study investigated maturational regulation of oxygen-sensitive developmental genes and proteins in developing mouse brain in relation to the degree of hypoxia. Methods: Physiological expression of HIF-1, CXCR4, SDF-1 and DCX were analyzed in the brain of C57/BL6 mice (P0–P60). In addition, mice (P0, P7) were exposed to normoxia, acute (8% O2, 6 h) or chronic hypoxia (10% O2, 7 d) followed by reoxygenation. Gene expression was analyzed by quantitative PCR, proteins were quantified by Western blot analysis and immunohistochemistry. Results: Cerebral HIF-1α protein, CXCR4 and DCX mRNA levels showed maturational stage-related peak levels at P0/P1, whereas SDF-1 mRNA levels were highest at P17. CXCR4 and SDF-1 mRNA levels were not altered in response to hypoxia. Whereas DCX mRNA levels significantly increased during acute hypoxia, down-regulation of DCX transcripts was found in response to chronic hypoxia compared to controls, and these changes were related to specifically vulnerable brain regions. Conclusions: Maturational stage-related dynamic changes of HIF-1α, CXCR4, SDF-1 and DCX may reflect involvement of hypoxia-regulated systems in important developmental regulatory processes of the developing brain. Extending the knowledge of differential effects of hypoxia on neurogenesis and dynamic regulatory networks present data provide a basis for future research on gestational age-specific neuroprotective options.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain and Development - Volume 34, Issue 4, April 2012, Pages 261–273
نویسندگان
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