title: Macroglial plasticity and the origins of reactive astroglia in experimental autoimmune encephalomyelitis.
abstract: Accumulations of hypertrophic, intensely glial fibrillary acidic protein-positive (GFAP(+)) astroglia, which also express immunoreactive nestin and vimentin, are prominent features of multiple sclerosis lesions. The issues of the cellular origin of hypertrophic GFAP(+)/vimentin(+)/nestin(+) "reactive" astroglia and also the plasticities and lineage relationships among three macroglial progenitor populations-oligodendrocyte progenitor cells (OPCs), astrocytes and ependymal cells-during multiple sclerosis and other CNS diseases remain controversial. We used genetic fate-mappings with a battery of inducible Cre drivers (Olig2-Cre-ER(T2), GFAP-Cre-ER(T2), FoxJ1-Cre-ER(T2) and Nestin-Cre-ER(T2)) to explore these issues in adult mice with myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis (EAE). The proliferative rate of spinal cord OPCs rose fivefold above control levels during EAE, and numbers of oligodendroglia increased as well, but astrogenesis from OPCs was rare. Spinal cord ependymal cells, previously reported to be multipotent, did not augment their low proliferative rate, nor give rise to astroglia or OPCs. Instead, the hypertrophic, vimentin(+)/nestin(+), reactive astroglia that accumulated in spinal cord in this multiple sclerosis model were derived by proliferation and phenotypic transformation of fibrous astroglia in white matter, and solely by phenotypic transformation of protoplasmic astroglia in gray matter. This comprehensive analysis of macroglial plasticity in EAE helps to clarify the origins of astrogliosis in CNS inflammatory demyelinative disorders.
authors.affiliation: Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, California 95817, USA.
authors.forename: Fuzheng
authors.initials: F
authors.lastname: Guo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maeda
authors.forename: Joyce
authors.initials: J
authors.lastname: Ma
authors.forename: Monica
authors.initials: M
authors.lastname: Delgado
authors.forename: Jiho
authors.initials: J
authors.lastname: Sohn
authors.forename: Laird
authors.initials: L
authors.lastname: Miers
authors.forename: Emily Mills
authors.initials: EM
authors.lastname: Ko
authors.forename: Peter
authors.initials: P
authors.lastname: Bannerman
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Wang
authors.forename: Chengji
authors.initials: C
authors.lastname: Zhou
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takebayashi
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology* / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009836:Oligodendroglia / Q000473:pathology* / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology