Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice.
The destiny of the mitotically active cells of the subventricular zone (SVZ) in adult rodents is to migrate to the olfactory bulb, where they contribute to the replacement of granular and periglomerular neurons. However, these adult neural progenitors also can be mobilized in periventricular white matter and triggered to differentiate into astrocytes and oligodendrocytes in response to lysolecithin-induced demyelination. To mimic the environmental conditions of multiple sclerosis, we assessed the proliferation, migration, and differentiation potential of adult SVZ progenitor cells in response to experimental autoimmune encephalomyelitis (EAE) in mice. Inflammation and demyelination were observed in all mouse brains after EAE induction. EAE induced cell proliferation throughout the brain and especially within the lesions. Proliferating cells were neural progenitors, astrocytes, and oligodendrocyte precursors. EAE enhanced the migration of SVZ-derived neural progenitors to the olfactory bulb and triggered their mobilization in the periventricular white matter. The mobilized cells gave rise to neurons, astrocytes, and oligodendrocytes in the olfactory bulb but essentially to astrocytes and oligodendrocytes in the lesioned white matter. Our data indicate that the adult mouse SVZ is a source of newly generated oligodendrocytes and thus may contribute, along with oligodendrocyte precursors, to the replacement of oligodendrocytes in inflammatory demyelinating diseases of the central nervous system such as multiple sclerosis.
Picard-Riera
Nathalie
N
Institut National de la Santé et de la Recherche Médicale U-546, Centre Hospitalier Universitaire Pitié-Salpêtrière, 105 Boulevard de l'Hôpital, 75634 Cedex 13, France.
Decker
Laurence
L
Delarasse
Cécile
C
Goude
Karine
K
Nait-Oumesmar
Brahim
B
Liblau
Roland
R
Pham-Dinh
Danielle
D
Baron-Van Evercooren
Anne
A
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002465:Cell Movement; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology*; D016548:Prosencephalon / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors
D001973:Bromodeoxyuridine