Effects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage. II. Neurochemical alterations and responses to pharmacological treatments.
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-HT(1a) and cortical 5-HT(2a) receptors in Lewis rats and downregulation of cortical 5-HT(2a) receptors in Fisher344 rats. BDV-associated regional downregulation of D(2) 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.
Pletnikov
Mikhail V
MV
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. pletnikov@cber.fda.gov
Rubin
Steven A
SA
Vogel
Michael W
MW
Moran
Timothy H
TH
Carbone
Kathryn M
KM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000820:Animal Diseases; D000818:Animals; D000831:Animals, Newborn; D001890:Borna Disease / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006220:Haloperidol / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D018377:Neurotransmitter Agents / Q000235:genetics* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D005473:Fluoxetine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol; D010134:Fenclonine; D004298:Dopamine; D009638:Norepinephrine