CD40 is expressed and functional on neuronal cells

Jun Tan, Terrence Town, Takashi Mori, Demian Obregon, Yajuan Wu, Anthony DelleDonne, Amyn Rojiani, Fiona Crawford, Richard A. Flavell, Mike Mullan

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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, immuno histochemistry 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-β removal from differentiated PC12 cells or serum withdrawal from primary cultured neurons. Importantly, CD40 ligation also protects neuronal cells from NGF-β 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-xL: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.

Original languageEnglish (US)
Pages (from-to)643-652
Number of pages10
JournalEMBO Journal
Volume21
Issue number4
DOIs
StatePublished - Feb 15 2002

Keywords

  • Apoptosis
  • CD40L
  • JNK
  • MAPK
  • Neuron

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'CD40 is expressed and functional on neuronal cells'. Together they form a unique fingerprint.

Cite this