کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8840579 | 1614690 | 2018 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Beta-hydroxybutyrate Promotes the Expression of BDNF in Hippocampal Neurons under Adequate Glucose Supply
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کلمات کلیدی
CREBDMEMGPRKBSBHBAHDACH3K27 acetylationJMJD3β-hydroxybutyrateBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز cAMP - cAMPG-protein-coupled receptor - G-پروتئین گیرندهbeta-hydroxybutyrate - بتا هیدروکسی بوتیراتKetone bodies - بدن کتونBrain-derived neurotrophic factor - فاکتور نوروتروفی مشتق شده از مغزDulbecco’s modified eagle’s medium - محیط عقاب اصلاح شده Dulbeccohistone deacetylase - هیستون داستیلازcAMP response element binding protein - پروتئین اتصال دهنده عنصر پاسخ cAMPHAT - کلاه
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Neurobiological evidence suggests that the ketone metabolite β-hydroxybutyrate (BHBA) exerts many neuroprotective functions for the brain. The previous study revealed that BHBA could promote the expression of brain-derived neurotrophic factor (BDNF) at glucose inadequate condition. Here we demonstrated that BHBA administration induced the expression of BDNF in the hippocampus of mice fed with normal diet. In vitro experiment results also showed that 0.02-2â¯mM BHBA significantly increased BDNF expression in both the primary hippocampal neurons and the hippocampus neuron cell line HT22 under adequate glucose supply. Bdnf transcription induced by BHBA stimulus was mediated through the cAMP/PKA-triggered phosphorylation of CREB (S133) and the subsequent up-regulation of histone H3 Lysine 27 acetylation (H3K27ac) binding at Bdnf promoters I, II, IV, and VI. Moreover, BHBA stimulus induced a decrease in tri-methylation of H3K27 (H3K27me3) binding at the Bdnf promoters II and VI and the elevation of H3K27me3-specific demethylase JMJD3, which also contributed to the activation of Bdnf transcription. These results demonstrated that BHBA within the physiological range could promote BDNF expression in neurons via a novel signaling function. Moreover, BHBA might possess more broad epigenetic regulatory activities, which affected both the acetylation and demethylation of H3K27. Our findings reinforce the beneficial effect of BHBA on the central nervous system (CNS) and suggest that BHBA administration with no need for energy restriction might also be a promising intervention to improve the neuronal activity and ameliorate the degeneration of CNS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 386, 21 August 2018, Pages 315-325
Journal: Neuroscience - Volume 386, 21 August 2018, Pages 315-325
نویسندگان
Hu Erling, Du Huan, Zhu Xinliang, Wang Leilei, Shang Sen, Wu Xingjuan, Lu Haixia, Lu Xiaoyun,