title: Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.
abstract: Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection.
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Guggenheim 442-D, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Buenz
authors.forename: Brian M
authors.initials: BM
authors.lastname: Sauer
authors.forename: Reghann G
authors.initials: RG
authors.lastname: Lafrance-Corey
authors.forename: Chandra
authors.initials: C
authors.lastname: Deb
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Denic
authors.forename: Christopher L
authors.initials: CL
authors.lastname: German
authors.forename: Charles L
authors.initials: CL
authors.lastname: Howe
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology* / Q000821:virology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010850:Picornaviridae Infections / Q000473:pathology*; D017966:Pyramidal Cells / Q000473:pathology* / Q000821:virology; D017945:Theilovirus