Neonatal viral infection decreases neuronal progenitors and impairs adult neurogenesis in the hippocampus.
While adult neurogenesis has been demonstrated in the hippocampal dentate gyrus of several mammalian species, including humans, the impact of viral infections has not been well studied. To examine this question we used a model in which neonatal rats are infected with lymphocytic choriomeningitis virus (LCMV) leading to a gradual loss of dentate granule cells (DGCs), which becomes fully evident in adulthood. Stereological cell counts performed 8 months after infection revealed that the loss of mature DGCs was accompanied by an 84.2% reduction in proliferation of DGCs as measured by BrdU uptake. Moreover, there was a severe loss of Mash1-labeled neuronal progenitor cells (87 and 83% decrease in the granule cell layer and hilus, respectively). Thus, neurogenesis is impaired in this model of chronic DGC loss, perhaps due to a virus-induced impoverishment of DGC neuronal progenitors. The LCMV model could be exploited to examine pathophysiological mechanisms of neurodegeneration and to test pharmacological strategies aimed at increasing neurogenesis or rescuing multipotent progenitors.
Sharma
Anup
A
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Valadi
Nojan
N
Miller
Andrew H
AH
Pearce
Bradley D
BD
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000821:virology*; D008216:Lymphocytic Choriomeningitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000378:metabolism / Q000821:virology*; D014157:Transcription Factors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C499318:Ascl1 protein, rat