Platelet-derived growth factor promotes repair of chronically demyelinated white matter.
In multiple sclerosis, remyelination becomes limited after repeated or prolonged episodes of demyelination. To test the effect of platelet-derived growth factor-A (PDGF-A) in recovery from chronic demyelination we induced corpus callosum demyelination using cuprizone treatment in hPDGF-A transgenic (tg) mice with the human PDGF-A gene under control of an astrocyte-specific promoter. After chronic demyelination and removal of cuprizone from the diet, remyelination and oligodendrocyte density improved significantly in hPDGF-A tg mice compared with wild-type mice. In hPDGF-A tg mice, oligodendrocyte progenitor density and proliferation values were increased in the corpus callosum during acute demyelination but not during chronic demyelination or the subsequent recovery period, compared with hPDGF-A tg mice without cuprizone or to treatment-matched wild-type mice. Proliferation within the subventricular zone and subcallosal zone was elevated throughout cuprizone treatment but was not different between hPDGF-A tg and wild-type mice. Importantly, hPDGF-A tg mice had reduced apoptosis in the corpus callosum during the recovery period after chronic demyelination. Therefore, PDGF-A may support oligodendrocyte generation and survival to promote remyelination of chronic lesions. Furthermore, preventing oligodendrocyte apoptosis may be important not only during active demyelination but also for supporting the generation of new oligodendrocytes to remyelinate chronic lesions.
Vana
Adam C
AC
Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
Flint
Nicole C
NC
Harwood
Norah E
NE
Le
Tuan Q
TQ
Fruttiger
Marcus
M
Armstrong
Regina C
RC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D003337:Corpus Callosum / Q000473:pathology*; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D003471:Cuprizone