Neurotrophin-3 specifically increases mature oligodendrocyte population and enhances remyelination after chemical demyelination of adult rat CNS.
In human central nervous system (CNS) demyelinating diseases, spontaneous remyelination is often incomplete. Therefore, we have tested whether neutrotrophin-3 (NT-3) accelerates CNS myelin repair after a chemically-induced demyelination. One group of adult rats was injected in the corpus callosum (CC) with 1 microl of 1% lysophosphatidylcholine (LPC) and 1 microl of NT-3 (1 microg/microl), and 15 days after injury (D15) remyelination was compared to control rats (receiving 1 microl of LPC+1 microl of vehicle buffer of NT-3). The demyelinated volume decreased by 56% in NT-3-treated rats at D15, and immunohistochemistry showed an increase in mature MBP(+) oligodendrocytes (OL) (+66%) in treated animals (whereas less mature (CNP(+)) OL were unchanged). Since less than 3% axons degenerate in this model, and as astrocytic gliosis was not modified, these data suggest that NT-3 acts directly on cells of the OL lineage to enhance remyelination in vivo.
Jean
Isabelle
I
Cell Biology Laboratory, UPRES EA 3143, University Hospital, 4 rue Larrey, F 49033 Angers cedex 01, France. isabelle.jean@med.univ-angers.fr
Lavialle
Céline
C
Barthelaix-Pouplard
Annick
A
Fressinaud
Catherine
C
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000473:pathology / Q000503:physiopathology; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D020933:Neurotrophin 3; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D001973:Bromodeoxyuridine