title: Down-regulation of brain-derived neurotrophic factor and its signaling components in the brain tissues of scrapie experimental animals.
abstract: Prion is a unique nucleic acid-free pathogen that causes human and animal fatal neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. There are two distinct classes of glycosylated receptors, neurotrophin receptor p75 (p75NTR) and tropomyosin-related kinase (Trk), that can bind to BDNF. To obtain insights into the possible alterations of brain BDNF and its signaling pathway in prion disease, the levels of BDNF and several molecules in the BDNF pathway in the brain tissues of scrapie agents 263K-infected hamsters were separately evaluated. Western blots and/or immunohistochemical (IHC) assays revealed that BDNF, TrkB, GRB2 and p75NTR, were significantly downregulated in the brain tissues of scrapie-infected rodents at terminal stage. Double-stained immunofluorescent assay (IFA) demonstrated that BDNF and phospho-TrkB predominately expressed in neurons. Dynamic analyses of the brain samples collected at the different time-points during the incubation period illustrated continuous decreases of BDNF, TrkB, phospho-TrkB, GRB2 and p75NTR, which correlated well with neuron loss. However, these proteins remained almost unchanged in the prion infected cell line SMB-S15 compared with those of its normal cell line SMB-PS. These data suggest that the BDNF signaling pathway is severely hindered in the brains of prion disease, which may contribute, at least partially, to the neuron death.
authors: School of Basic Medical Sciences, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, People's Republic of China; State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Ting-Ting
authors: TT
authors: Wang
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China; Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors: Chan
authors: C
authors: Tian
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Jing
authors: J
authors: Sun
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Hui
authors: H
authors: Wang
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Bao-Yun
authors: BY
authors: Zhang
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Cao
authors: C
authors: Chen
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Jing
authors: J
authors: Wang
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Kang
authors: K
authors: Xiao
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Li-Na
authors: LN
authors: Chen
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Yan
authors: Y
authors: Lv
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Chen
authors: C
authors: Gao
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China.
authors: Qi
authors: Q
authors: Shi
authors: School of Basic Medical Sciences, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, People's Republic of China. Electronic address: xinyan_2505@126.com.
authors: Yan
authors: Y
authors: Xin
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, People's Republic of China; Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China. Electronic address: dongxp238@sina.com.
authors: Xiao-Ping
authors: XP
authors: Dong
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D015536:Down-Regulation; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051380:GRB2 Adaptor Protein; D010750:Phosphoproteins; D017475:Receptors, Nerve Growth Factor; D020813:Receptor, trkB
keywords: BDNF; GRB2; Prion diseases; Scrapie; TrkB; p75NTR