Scientific Publications by FDA Staff

J Neurovirol 2004 Oct;10(5):267-77

Developmental alterations in serotoninergic neurotransmission in Borna disease virus (BDV)-infected rats: a multidisciplinary analysis.

Dietz D, Vogel M, Rubin S, Moran T, Carbone K, Pletnikov M

Pletnikov MV, Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA CBER, US FDA, Bethesda, MD USA

Neonatal Borna disease virus (BDV) infection of the rat brain serves as a valuable model for studying the pathogenesis of neurodevelopmental abnormalities following early brain injury. Previous experiments have demonstrated significant alterations in regional tissue content of serotonin (5-HT) in neonatally BDV-infected Lewis rats. The present study sought to provide more insights into postnatal virus-associated alterations in 5-HT neurotransmission by evaluating the density of 5-HT1a receptors in the hippocampus and 5-HT2a receptors in the cortex, regional 5-HT tissue concentrations, behavioral responses to a 5-HT agonist, quipazine, and numbers of neurons in specific subfields of the hippocampus on days 7, 14, and 30 after neonatal BDV infection in Lewis rats. Neonatal BDV infection was found to be associated with a gradual increase in the density of 5-HT2a and 5-HT1a postsynaptic receptors followed by an elevation of 5-HT contents at both the levels of synaptic terminals (i.e., cortex and hippocampus) and cell bodies (i.e., raphe nuclei). In addition, there was an enhanced behavioral response to quipazine. Virus-associated neurochemical and behavioral changes were accompanied by a decline in the number of neurons in the dentate gyrus and in the CA1 field of the hippocampus. No change in the number of neurons in the CA3/2 field of the hippocampus was observed. The present pattern of BDV-associated alterations in 5-HT brain system along with available data from other laboratories suggest that BDV might compromise axonal transport and/or release of 5-HT, resulting in decreased 5-HT neurotransmission.