Interleukin-1 mediates long-term hippocampal dentate granule cell loss following postnatal viral infection.

TitleInterleukin-1 mediates long-term hippocampal dentate granule cell loss following postnatal viral infection.
Publication TypeJournal Article
Year of Publication2010
AuthorsOrr AG, Sharma A, Binder NB, Miller AH, Pearce BD
JournalJ Mol Neurosci
Volume41
Issue1
Pagination89-96
Date Published2010 May
ISSN1559-1166
KeywordsAnimals, Animals, Newborn, Dentate Gyrus, Humans, Interleukin 1 Receptor Antagonist Protein, Interleukin-1beta, Lymphocytic Choriomeningitis, Rats, Rats, Inbred Lew
Abstract

Viral infections of the developing CNS can cause long-term neuropathological sequela through undefined mechanisms. Proinflammatory cytokines such as IL-1beta have gained attention in mediating neurodegeneration in corticohippocampal structures due to a variety of insults in adults, though there is less information on the developing brain. Little is known concerning the spatial-temporal pattern of IL-1beta induction in the developing hippocampus following live virus infection, and there are few studies addressing the long-term consequences of this cytokine induction. We report that infection of rats with lymphocytic choriomeningitis virus on postnatal day 4 induces IL-1beta protein in select regions of the hippocampus on 6, 15, 21, and 45 days after infection. This infection resulted in a 71% reduction of dentate granule cell neurons by the time the rats reached mid-adulthood. We further investigated the causative role of IL-1 in this dentate granule cell loss by blocking IL-1 activity using an IL-1ra-expressing adenoviral vector administered at the time of infection. Blockade of IL-1 abrogated the infection-associated neuron loss in this vivo model. Considering that IL-1 can be triggered by multiple perinatal insults, our findings suggest that early therapy with anti-inflammatory agents that block IL-1 may be effective for reducing adulthood neuropathology.

DOI10.1007/s12031-009-9293-5
Alternate JournalJ. Mol. Neurosci.
PubMed ID19774496
Grant List5R29NS037068 / NS / NINDS NIH HHS / United States