title: CD40 is expressed and functional on neuronal cells.
abstract: We show here that CD40 mRNA and protein are expressed by neuronal cells, and are increased in differentiated versus undifferentiated N2a and PC12 cells as measured by RT-PCR, western blotting and immunofluorescence staining. Additionally, immunohistochemistry reveals that neurons from adult mouse and human brain also express CD40 in situ. CD40 ligation results in a time-dependent increase in p44/42 MAPK activation in neuronal cells. Furthermore, ligation of CD40 opposes JNK phosphorylation and activity induced by NGF-beta removal from differentiated PC12 cells or serum withdrawal from primary cultured neurons. Importantly, CD40 ligation also protects neuronal cells from NGF-beta or serum withdrawal-induced injury and affects neuronal differentiation. Finally, adult mice deficient for the CD40 receptor demonstrate neuronal dysfunction as evidenced by decreased neurofilament isoforms, reduced Bcl-x(L):Bax ratio, neuronal morphological change, increased DNA fragmentation, and gross brain abnormality. These changes occur with age, and are clearly evident at 16 months. Taken together, these data demonstrate a role of CD40 in neuronal development, maintenance and protection in vitro and in vivo.
authors.affiliation: The Roskamp Institute, Department of Psychiatry, University of South Florida, 3515 East Fletcher Avenue, Tampa, FL 33613, USA. jtan@hsc.usf.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.forename: Demian
authors.initials: D
authors.lastname: Obregon
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Anthony
authors.initials: A
authors.lastname: DelleDonne
authors.forename: Amyn
authors.initials: A
authors.lastname: Rojiani
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Mike
authors.initials: M
authors.lastname: Mullan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019013:CD40 Antigens; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases