Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse.
Proliferation of the adult NG2-expressing oligodendrocyte precursor cells has traditionally been viewed as a remyelination response ensuing from destruction of myelin and oligodendrocytes, and not to the axonal pathology that is also a characteristic of demyelinating disease. To better understand the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed by a reduction of cellular NG2 expression to subnormal levels from day 5 to 7 and reappearance of normal appearing NG2+ cells from day 10. Mice that had received repeated injections of bromodeoxyuridine from 24 to 72 h after surgery contained significant numbers of bromodeoxyuridine-incorporating oligodendrocytes in the areas with axonal degeneration at day 7. The results suggest that axonal degeneration induces a unique sequence of changes of NG2+ cells and that a subpopulation of the newly generated NG2+ cells differentiate into oligodendrocytes.
Nielsen
Helle H
HH
Medical Biotechnology Centre, University of Southern Denmark, Odense, Denmark.
Ladeby
Rune
R
Drøjdahl
Nina
N
Peterson
Alan C
AC
Finsen
Bente
B
D000818:Animals; D000941:Antigens / Q000096:biosynthesis* / Q000235:genetics; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4