title: Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway.
abstract: Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca2+imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca2+]ilevel, Bdnf mRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca2+release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca2+) stores. Blockade of Ca2+increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken together, these findings establish the Ca2+-ERK-CREB cascade as a potential signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca2+-dependent Bdnf mRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Juanfang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cadet Brigade, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China.
authors.forename: Siguo
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China. qianjixianxj@126.com.
authors.forename: Jixian
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China. sunhonghuifmmu@126.com.
authors.forename: Honghui
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004789:Enzyme Activation / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D028022:Low-Level Light Therapy; D008954:Models, Biological; D055495:Neurogenesis / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000528:radiation effects*; D014158:Transcription, Genetic / Q000528:radiation effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D015544:Inositol 1,4,5-Trisphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium
keywords: Brain-derived neurotrophic factor; Calcium; Extracellular signal-regulated kinase; Low-level laser; cAMP-response element binding protein