Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis.
Multiple sclerosis is an inflammatory disease of the central nervous system characterized by inflammation, demyelination, axonal degeneration and accumulation of neurological disability. Previously, we demonstrated that stem cells constitute a possible endogenous source for remyelination. We now addressed the question of whether neurogenesis can occur in neuroinflammatory lesions. We demonstrated that, in experimental autoimmune encephalomyelitis, induced in rats 1,1'-dioctadecyl-6,6'-di(4sulphopentyl)-3,3,3',3'tetramethylindocarbocyanin(DiI)-labelled ependymal cells not only proliferated but descendants migrated to the area of neuroinflammation and differentiated into cells expressing the neuronal markers beta-III-tubulin and NeuN. Furthermore, these cells were immunoreactive for bromodeoxyuridine and PCNA, markers for cells undergoing cell proliferation. Using the whole-cell patch-clamp technique on freshly isolated 1, DiI-labelled cells from spinal cord lesions we demonstrated the ability of these cells to fire overshooting action potentials similar to those of immature neurones. We thus provide the first evidence for the initiation of neurogenesis in neuroinflammatory lesions in the adult spinal cord.
Danilov
Alexandre I
AI
Department of Clinical Neuroscience, Karolinska Instiutet, Sweden. alexandre.danilov@cmm.ki.se
Covacu
Ruxandra
R
Moe
Morten C
MC
Langmoen
Iver A
IA
Johansson
Clas B
CB
Olsson
Tomas
T
Brundin
Lou
L
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002232:Carbocyanines; D002454:Cell Differentiation / Q000502:physiology; D049108:Cell Enlargement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D018613:Microscopy, Confocal / Q000379:methods; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D018809:Proliferating Cell Nuclear Antigen; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine