Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate.
Myelinogenesis in the mammal nervous system occurs predominantly postnatally. Glatiramer acetate (GA), a drug for the treatment for multiple sclerosis (MS), has been shown to induce immunomodulation and neuroprotection in the inflamed CNS in MS and in experimental autoimmune encephalomyelitis (EAE). Here we investigated whether GA can affect myelinogenesis and oligodendrogenesis in the developing nervous system under nonpathological conditions. Towards this end we studied myelination in mice injected daily by GA, at postnatal Days 7-21. Immunohistological and ultrastructural analyses revealed significant elevation in the number of myelinated axons as well as in the thickness of the myelin encircling them and their resulting g-ratios, in spinal cords of GA-injected mice compared with their PBS-injected littermates, at postnatal Day 14. Elevation in myelinated axons was detected also in the peripheral ventral roots of the motor nerves. GA induced also an increase in axonal diameter, implying an effect on the overall development of the nervous system. A prominent elevation in the amount of progenitor oligodendrocytes and their BrdU incorporation, as well as in mature oligodendrocytes indicated that the effect of GA is linked to increased proliferation and differentiation along the oligodendroglial maturation cascade. In addition, elevation in insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) was found in the white matter of the GA-injected mice. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates at postnatal Day 21. These cumulative findings corroborate the beneficial effect of GA on oligodendrogenesis and myelination.
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel, 76100.
Renana
R
From
Raya
R
Eilam
Dekel D
DD
Bar-Lev
Smadar
S
Levin-Zaidman
Michael
M
Tsoory
Patrizia
P
LoPresti
Michael
M
Sela
Ruth
R
Arnon
Rina
R
Aharoni
D000818:Animals; D051379:Mice; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D038081:Organogenesis / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors; D009103:Multiple Sclerosis; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents; D007334:Insulin-Like Growth Factor I; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D010455:Peptides; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C512773:Olig2 protein, mouse
myelination; oligodendrocyte proliferation and differentiation; postnatal development