Neurobiology of LCM virus infection in rodents

In addition to the previously reported data on the retinal and cerebellar immunopathology following infection of neonatal rats with LCM virus, we have found that there are long-term effects on behavioural and neurological development. Rats were inoculated intracerebrally with the E-350 strain at different ages during the first 3 weeks after birth. Behavioural tests were initiated when the animals were either 3 months or 1 year of age. The behavioural consequences appear to be a long-term alteration in emotional reactivity such that the infected animals are less responsive than controls as assessed by these measures. No alterations were detected in animals infected after the first postnatal week. Complementing these data are the findings of a collaterally progressive lesion of the hippocampal dentate gyrus as well as a loss in total cell number in the forebrain (as assessed by DNA, RNA, and protein determinations) amounting to about 20% of the brain mass. These behavioural, histological, and biochemical data indicate that there are forebrain structures, most probably within the limbic system, that are susceptible at critical phases of development to the pathological consequences of infection with LCM virus.