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.
Similar content being viewed by others
References
Alexander GM, Deitch JS, Seeburger JL, Del Valle L, Heiman-Patterson TD (2000). Elevated cortical extracellular fluid glutamate in transgenic mice expressing human mutant (G93A) Cu/Zn superoxide dismutase. J Neurochem 74: 1666–1673.
Anderson CM, Swanson RA (2000). Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32: 1–14.
Baker DA, Xi ZX, Shen H, Swanson CJ, Kalivas PW (2002). The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci 22: 9134–9141.
Bautista JR, Rubin SA, Moran TH, Schwartz GJ, Carbone KM (1995). Developmental injury to the cerebellum following perinatal borna disease virus infection. Brain Res Dev Brain Res 90: 45–53.
Billaud JN, Ly C, Phillips TR, de la Torre JC (2000). Borna disease virus persistence causes inhibition of glutamate uptake by feline primary cortical astrocytes. J Virol 74: 10438–10446.
Briese T, Hornig M, Lipkin WI (1999). Bornavirus immunopathogenesis in rodents: models for human neurological diseases. J NeuroVirol 5: 604–612.
Carbone KM, Park SW, Rubin SA, Waltrip RW 2nd, Vogelsang GB (1991). Borna disease: association with a maturation defect in the cellular immune response. J Virol 65: 6154–6164.
Chen Y, Swanson RA (2003). Astrocytes and brain injury. J Cereb Blood Flow Metab 23: 137–149.
Danbolt NC (2001). Glutamate uptake. Prog Neurobiol 65: 1–105.
de la Torre JC (2002). Bornavirus and the brain. J Infect Dis 186(Suppl 2): S241-S247.
Deitch JS, Alexander GM, Del Valle L, Heiman-Patterson TD (2002). GLT-1 glutamate transporter levels are unchanged in mice expressing G93A human mutant SOD1. J Neurol Sci 193: 117–126.
Dietz D, Vogel M, Rubin S, Moran T, Carbone K, Pletnikov M (2004). Developmental alterations in serotoninergic neurotransmission in Borna disease virus (BDV)-infected rats: a multidisciplinary analysis. J Neurovirol 10: 267–277.
Eisenman LM, Brothers R, Tran MH, Kean RB, Dickson GM, Dietzschold B, Hooper DC (1999). Neonatal borna disease virus infection in the rat causes a loss of purkinje cells in the cerebellum. J NeuroVirol 5: 181–189.
Espey MG, Kustova Y, Sei Y, Basile AS (1998). Extracellular glutamate levels are chronically elevated in the brains of LP-BM5-infected mice: a mechanism of retrovirusinduced encephalopathy. J Neurochem 71: 2079–2087.
Gochenauer GE, Robinson MB (2001). Dibutyryl-cAMP (db-cAMP) up-regulates astrocytic chloride-dependent L-[3H]glutamate transport and expression of both system xc(−) subunits. J Neurochem 78: 276–286.
Gonzalez-Dunia D, Sauder C, de la Torre JC (1997). Borna disease virus and the brain. Brain Res Bull 44: 647–664.
Gonzalez-Dunia D, Watanabe M, Syan S, Mallory M, Masliah E, De La Torre JC (2000). Synaptic pathology in borna disease virus persistent infection. J Virol 74: 3441–3448.
Gonzalez-Dunia D, Volmer R, Mayer D, Schwemmle M. (2005). Borna disease virus interference with neuronal plasticity. Virus Res 111: 224–234.
Gosztonyi G, Ludwig H (1984). Neurotrasnmitter receptors and vial neurotropism. Neuropsychiatr Clin 3: 107–114.
Gosztonyi G, Ludwig H (1995). Borna disease—neuropathology and pathogenesis. Curr Top Microbiol Immunol 190: 39–73.
Gosztonyi G, Ludwig H (2001). Interaction of viral proteins with neurotransmitter receptors may protect or destroy neurons. Curr Top Microbiol Immunol 253: 121–144.
Haas B, Becht H, Rott R (1986). Purification and properties of an intranuclear virus-specific antigen from tissue infected with Borna disease virus. J Gen Virol 67(Pt 2): 235–241.
Hara MR, Snyder SH (2006). Cell signaling and neuronal death. Annu Rev Pharmacol Toxicol.
Hornig M, Chian D, Sindelar M, Hoffman K, Lipkin WI (2001). AMPA receptor disturbances and apoptosis in a rodent model of neurodevelopemtnal damage. Program, 1st Annual International Meeting for Autism Research, San Diego, CA, 2001, p B-49, Abstract no. 21.02.
Hornig M, Weissenbock H, Horscroft N, Lipkin WI (1999). An infection-based model of neurodevelopmental damage. Proc Natl Acad Sci U S A 96: 12102–12107.
Kaul M, Lipton SA (2006). Mechanisms of neuronal injury and death in HIV-1 associated dementia. Curr HIV Res 4: 307–318.
Maragakis NJ, Rothstein JD (2004). Glutamate transporters: animal models to neurologic disease. Neurobiol Dis 15: 461–473.
McBean GJ (2002). Cerebral cystine uptake: a tale of two transporters. Trends Pharmacol Sci 23: 299–302.
Melendez RI, Vuthiganon J, Kalivas PW (2005). Regulation of extracellular glutamate in the prefrontal cortex: Focus on the cystine glutamate exchanger and group I metabotropic glutamate receptors. J Pharmacol Exp Ther 314: 139–147.
Mitchell IJ, Cooper AJ, Griffiths MR (1999). The selective vulnerability of striatopallidal neurons. Prog Neurobiol 59: 691–719.
Nyitrai G, Kekesi KA, Juhasz G (2006). Extracellular level of GABA and Glu: in vivo microdialysis-HPLC measurements. Curr Top Med Chem 6: 935–940.
Pasantes-Morales H (1996). Volume regulation in brain cells: cellular and molecular mechanisms. Metab Brain Dis 11: 187–204.
Paxinos Watson (1986). The rat brain in stereotaxic coordinates, 2nd ed. New York: Academic Press.
Pletnikov MV, Moran TH, Carbone KM (2002a). Borna disease virus infection of the neonatal rat: Developmental brain injury model of autism spectrum disorders. Front Biosci 7: d593-d607.
Pletnikov MV, Rubin SA, Vogel MW, Moran TH, Carbone KM (2002b). Effects of genetic background on neonatal borna disease virus infection-induced neurodevelopmental damage. I. brain pathology and behavioral deficits. Brain Res 944: 97–107.
Richt JA, Rott R (2001). Borna disease virus: a mystery as an emerging zoonotic pathogen. Vet J 161: 24–40.
Sauder C, de la Torre JC (1999). Cytokine expression in the rat central nervous system following perinatal borna disease virus infection. J Neuroimmunol 96: 29–45.
Sonsalla PK, Albers DS, Zeevalk GD (1998). Role of glutamate in neurodegeneration of dopamine neurons in several animal models of parkinsonism. Amino Acids 14: 69–74.
Tang XC, Kalivas PW (2003). Bidirectional modulation of cystine/glutamate exchanger activity in cultured cortical astrocytes. Ann N Y Acad Sci 1003: 472–475.
Timmerman W, Westerink BH (1997). Brain microdialysis of GABA and glutamate: what does it signify? Synapse 27: 242–261.
Tomonaga K, Kobayashi T, Ikuta K (2002). Molecular and cellular biology of borna disease virus infection. Microbes Infect 4: 491–500.
Weissenbock H, Hornig M, Hickey WF, Lipkin WI (2000). Microglial activation and neuronal apoptosis in bornavirus infected neonatal lewis rats. Brain Pathol 10: 260–272.
West MJ (1993). New stereological methods for counting neurons. J Neuropathol Exp Neurol 14: 275–285.
Williams BL, Lipkin WI (2006). Endoplasmic reticulum stress and neurodegeneration in rats neonatally infected with borna disease virus. J Virol 80: 8613–8626.
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was supported by R01MH048948.
Rights and permissions
About this article
Cite this article
Ovanesov, M.V., Vogel, M.W., Moran, T.H. et al. Neonatal Borna disease virus infection in rats is associated with increased extracellular levels of glutamate and neurodegeneration in the striatum. Journal of NeuroVirology 13, 185–194 (2007). https://doi.org/10.1080/13550280701258415
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1080/13550280701258415