title: Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways.
abstract: Low-intensity pulsed ultrasound (LIPUS) stimulation has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in astrocytes of an in vitro model and rat brains of an in vivo model; however, their molecular mechanisms are still not well clarified. Here, we investigated the underlying mechanisms of BDNF enhancement by LIPUS in rat cerebral cortex astrocytes. After LIPUS stimulation in astrocytes, the protein and mRNA expressions were measured by western blot and RT-PCR, respectively. The concentration of intracellular calcium was determined spectrophotometrically. The results showed that LIPUS enhanced the phosphorylation of tropomyosin-related kinase B (TrkB) and Akt but had no effect on Erk1/2 phosphorylation. Additionally, LIPUS increased the intracellular concentration of calcium and enhanced the protein levels of calmodulin-dependent kinase (CaMK) II and CaMKIV. LIPUS also activated the phosphorylation of NF-κB-p65 but did not promote the activation of cAMP response element-binding protein (CREB). Taken together, our results suggest that LIPUS stimulation upregulates BDNF production in astrocytes through the activation of NF-κB via the TrkB/PI3K/Akt and calcium/CaMK signaling pathways. BDNF has emerged as a major molecular player in the regulation of neural circuit development and function. Therefore, LIPUS stimulation may play a crucial and beneficial role in neurodegenerative diseases.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Lai
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Bo-Lin
authors.initials: BL
authors.lastname: Chen
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences.|Biophotonics and Molecular Imaging Research Center.|Biomedical Engineering Research and Development Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000528:radiation effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D002540:Cerebral Cortex / Q000166:cytology; D004789:Enzyme Activation / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D000069453:Ultrasonic Waves
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050882:CREB-Binding Protein; D002118:Calcium; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D020813:Receptor, trkB; C000621230:Ntrk2 protein, rat
keywords: BDNF; NF-κB; TrkB; calcium; ultrasound