Effects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage: II. Neurochemical alterations and responses to pharmacological treatments

Mikhail V. Pletnikov, Steven A. Rubin, Michael W. Vogel, Timothy H. Moran, Kathryn M. Carbone

Research output: Contribution to journalArticlepeer-review

Abstract

The gene-environment interplay is thought to determine variability in clinical conditions and responses to therapy in human neurodevelopmental disorders. Studying abnormal brain and behavior development in inbred strains of rodents can help in the identification of the complex pathogenic mechanisms of the host-environment interaction. This paper is the second one in a series of the two reports of the use of the Borna disease virus (BDV) infection model of neurodevelopmental damage to characterize effects of genetic background on virus-induced neurodevelopmental damage in inbred rat strains, Lewis and Fisher344. The present data demonstrate that neonatal BDV infection produced regional and strain-related alterations in levels of serotonin, norepinephrine and in levels of serotonin turnover at postnatal day 120. Neonatal BDV infection also induced upregulation of hippocampal 5-HT1a and cortical 5-HT2a receptors in Lewis rats and downregulation of cortical 5-HT2a receptors in Fisher344 rats. BDV-associated regional downregulation of D2 receptors and dopamine transporter sites were noted in Fisher344 rats. In addition to the neurochemical disturbances, neonatal BDV infection induced differential responses to serotonin compounds. While 8-OH-DPAT suppressed virus-enhanced ambulation in BDV-infected Fisher344, fluoxetine inhibited virus-induced hyperactivity in BDV-infected Lewis rats only. The present data provide new insights into the pathogenic events that lead to differential responses to pharmacological treatments in genetically different animals following exposure to the same environmental challenge.

Original languageEnglish (US)
Pages (from-to)108-123
Number of pages16
JournalBrain research
Volume944
Issue number1-2
DOIs
StatePublished - Jul 19 2002

Keywords

  • 8-OH-DPAT
  • Borna
  • Fisher344
  • Fluoxetine
  • Lewis
  • Monoamine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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