• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Experimental autoimmune encephalomyelitis repressed by microglial paralysis.

Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.

Pubmed ID: 15665833

Authors

  • Heppner FL
  • Greter M
  • Marino D
  • Falsig J
  • Raivich G
  • Hövelmeyer N
  • Waisman A
  • Rülicke T
  • Prinz M
  • Priller J
  • Becher B
  • Aguzzi A

Journal

Nature medicine

Publication Data

February 4, 2005

Associated Grants

None

Mesh Terms

  • Animals
  • Antigens, CD11b
  • Antiviral Agents
  • Bone Marrow Cells
  • Brain
  • Chimera
  • Encephalomyelitis, Autoimmune, Experimental
  • Facial Nerve
  • Ganciclovir
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Microglia
  • Recombinant Fusion Proteins
  • Simplexvirus
  • Thymidine Kinase