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Age-related changes in susceptibility of rat brain slice cultures including hippocampus to encephalomyocarditis virus
W Su1, A Ueno-Yamanouchi, K Uetsuka
1Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. aa77170@mail.ecc.u-tokyo.ac.jp
Abstract:
Replication of the D variant of encephalomyocarditis virus (EMC-D) and its cytopathic effects were studied in the brain slice cultures including hippocampus (hippocampal slice) obtained from postnatal 1-, 4-, 7-, 14-, 28-and 56-day-old Fischer 344 rats. At 0, 12, 24, 36 and 48 h after infection, virus titres of the slices and culture media were assayed. Viral replication was observed in cultures from 1-to 28-day-old rats, and the highest titre was recorded in the slice and culture medium from the youngest rat. The peak of virus titre decreased with age and no distinct viral replication was observed in the cultures from 56-day-old rats. Light microscopy revealed that degenerative and necrotic changes appeared in the infected hippocampal slices from 1- to 28-day-old rats, and the changes became less prominent with age. In situ hybridization and indirect immunofluorescence staining showed that positive signals of viral RNA and antigen were prominent in younger rats and decreased with age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC-D is less related to the maturation of the immune system but possibly to that of the neurone.
Insights
Encephalomyocarditis virus (EMC-D) replication and brain damage decrease with age in Fischer 344 rats. Neuronal maturation, not the immune system, likely explains this reduced susceptibility in older rats.
Area of Science:
- Neuroscience
- Virology
- Developmental Biology
Background:
- Encephalomyocarditis virus (EMC-D) can infect the central nervous system.
- Understanding age-related susceptibility to viral infections in the brain is crucial.
Purpose of the Study:
- To investigate the age-dependent replication and cytopathic effects of EMC-D in rat hippocampal slice cultures.
- To determine if neuronal or immune system maturation underlies age-related changes in viral susceptibility.
Main Methods:
- Primary hippocampal slice cultures from Fischer 344 rats aged 1 to 56 days were infected with EMC-D.
- Virus titration, light microscopy, in situ hybridization, and indirect immunofluorescence staining were performed at various time points post-infection.
Main Results:
- Viral replication and cytopathic effects were observed in cultures from rats up to 28 days old, with the highest levels in the youngest (1-day-old) rats.
- Viral RNA and antigen signals were prominent in younger rats and decreased significantly with age.
- Degenerative changes in hippocampal slices were age-dependent, becoming less severe in older rats.
Conclusions:
- Rat brain susceptibility to EMC-D infection decreases with age.
- This age-related decrease is likely due to neuronal maturation rather than immune system development.