title: Modulation of neural stem/progenitor cell proliferation during experimental Herpes Simplex encephalitis is mediated by differential FGF-2 expression in the adult brain.
abstract: Neural stem cells (NSCs) respond to inflammatory cues induced during brain injury and are thought to be involved in recovery from brain damage. Little is known about NSC response during brain infections. The present study evaluated NSC proliferation during Herpes Simplex Virus-1 brain infection. Total numbers of nestin(+) NSCs increased significantly in infected brains at 6 days post infection (p.i.). However, by 15 days p.i. the nestin(+) population decreased significantly below levels observed in uninfected brains and remained depressed through 30 days p.i. This initial increase in NSC population occurred concurrently with increased brain cell proliferation, which peaked at 3 days p.i. On closer examination, we found that while actively proliferating Sox2(+) NSCs increased in number at 6 days p.i., proliferating DCX(+) neuroblasts contributed to the increased response at 3 days p.i. However, overall proliferation decreased steadily from 15 days p.i. to below control levels. To determine the mechanisms involved in altering NSC proliferation, neurotrophin and growth factor expression profiles were assessed. FGF-2 gene expression increased at 5 days p.i. and was robustly down-regulated at 15 days p.i. (>1000-fold), which was further confirmed by increased FGF-2 immunostaining around the lateral ventricles. Furthermore, supplementing infected animals with recombinant FGF-2, at 15 days p.i., significantly increased the number of proliferating brain cells. These findings demonstrate that the temporal changes in NSC proliferation are mediated through the regulation of FGF-2 and that the NSC niche may benefit from supplementation with FGF-2 during HSV-1 brain infection.
authors.affiliation: Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Rotschafer
authors.forename: Shuxian
authors.initials: S
authors.lastname: Hu
authors.forename: Morgan
authors.initials: M
authors.lastname: Little
authors.forename: Melissa
authors.initials: M
authors.lastname: Erickson
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.forename: Maxim C J
authors.initials: MC
authors.lastname: Cheeran
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000821:virology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000166:cytology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004622:Embryo, Mammalian; D020803:Encephalitis, Herpes Simplex / Q000473:pathology* / Q000601:surgery; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000378:metabolism*; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D019394:Ki-67 Antigen / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D064231:Nestin; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D016222:Fibroblast Growth Factor 2; D017493:Leukocyte Common Antigens
keywords: Adult neurogenesis; FGF-2; Herpes Simplex encephalitis; Neural stem cells; Proliferation