Abstract
The authors evaluated a role of glutamate (GLU) excitotoxicity in neonatal Borna disease virus (BDV) infection–associated neuronal injury by measuring extracellular levels of GLU in the striatum of 70-day-old Fischer344 rats using in vivo microdialysis. The effects of BDV infection on the protein levels of the GLU transporters and the cystine-GLU antiporter and on the total numbers of striatal neurons and the volume of the striatum were also assessed. BDV increased the basal levels of GLU but did not change those of aspartate, glutamine, or taurine. BDV infection did not alter the effects of a blockade of GLU transporters but attenuated the effects of an inhibition of the cystine-GLU antiporter, without affecting the protein levels of the GLU transporters. The elevated levels of GLU were associated with decreased neuronal numbers and volume in the striatum. The present data are the first in vivo evidence that GLU excitotoxicity might contribute to BDV-associated neuronal injury in the striatum.
The authors would like to thank Dr. Thomas Guilarte (JHU Bloomberg School of Public Health) for his generous help with the microdialysis equipment. The authors are grateful to Steven Rubin, MA, and Christian Sauder, PhD (U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Bethesda, MD) for helpful comments on the revised manuscript. This study was supported by R01MH048948.