کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6017039 | 1580156 | 2016 | 25 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cognitive impairments following cranial irradiation can be mitigated by treatment with a tropomyosin receptor kinase B agonist
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کلمات کلیدی
ERKDcxPSD-95TrkBSGZDHFpost-synaptic density 957,8-Dihydroxyflavone - 7،8-دی هیدروکسی فلاونBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز Akt - آکتBrdU - بروموداکسی اوریدینbromodeoxyuridine - برومودسوویریدینBrain-derived neurotrophic factor - فاکتور نوروتروفی مشتق شده از مغزsubgranular zone - منطقه غده گرانولیprotein kinase B - پروتئین کیناز Bextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Brain radiotherapy is frequently used successfully to treat brain tumors. However, radiotherapy is often associated with declines in short-term and long-term memory, learning ability, and verbal fluency. We previously identified a downregulation of the brain-derived neurotrophic factor (BDNF) following cranial irradiation in experimental animals. In the present study, we investigated whether targeting the BDNF high affinity receptor, tropomysin receptor kinase B (TrkB), could mitigate radiation-induced cognitive deficits. After irradiation, chronic treatment with a small molecule TrkB agonist, 7,8-dihydroxyflavone (DHF) in mice led to enhanced activation of TrkB and its downstream targets ERK and AKT, both important factors in neuronal development. DHF treatment significantly restored spatial, contextual, and working memory, and the positive effects persisted for at least 3Â months after completion of the treatment. Consistent with preservation of cognitive functions, chronic DHF treatment mitigated radiation-induced suppression of hippocampal neurogenesis. Spine density and major components of the excitatory synapses, including glutamate receptors and postsynaptic density protein 95 (PSD-95), were also maintained at normal levels by DHF treatment after irradiation. Taken together, our results show that chronic treatment with DHF after irradiation significantly mitigates radiation-induced cognitive defects. This is achieved most likely by preservation of hippocampal neurogenesis and synaptic plasticity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 279, May 2016, Pages 178-186
Journal: Experimental Neurology - Volume 279, May 2016, Pages 178-186
نویسندگان
Phillip Yang, David Leu, Keqiang Ye, Chandra Srinivasan, John R. Fike, Ting-Ting Huang,