Effects of progesterone on oligodendrocyte progenitors, oligodendrocyte transcription factors, and myelin proteins following spinal cord injury.
Progesterone is emerging as a myelinizing factor for central nervous system injury. Successful remyelination requires proliferation and differentiation of oligodendrocyte precursor cells (OPC) into myelinating oligodendrocytes, but this process is incomplete following injury. To study progesterone actions on remyelination, we administered progesterone (16 mg/kg/day) to rats with complete spinal cord injury. Rats were euthanized 3 or 21 days after steroid treatment. Short progesterone treatment (a) increased the number of OPC without effect on the injury-induced reduction of mature oligodendrocytes, (b) increased mRNA and protein expression for the myelin basic protein (MBP) without effects on proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG), and (c) increased the mRNA for Olig2 and Nkx2.2 transcription factors involved in specification and differentiation of the oligodendrocyte lineage. Furthermore, long progesterone treatment (a) reduced OPC with a concomitant increase of oligodendrocytes; (b) promoted differentiation of cells that incorporated bromodeoxyuridine, early after injury, into mature oligodendrocytes; (c) increased mRNA and protein expression of PLP without effects on MBP or MOG; and (d) increased mRNA for the Olig1 transcription factor involved in myelin repair. These results suggest that early progesterone treatment enhanced the density of OPC and induced their differentiation into mature oligodendrocytes by increasing the expression of Olig2 and Nkx2.2. Twenty-one days after injury, progesterone favors remyelination by increasing Olig1 (involved in repair of demyelinated lesions), PLP expression, and enhancing oligodendrocytes maturation. Thus, progesterone effects on oligodendrogenesis and myelin proteins may constitute fundamental steps for repairing traumatic injury inflicted to the spinal cord.
Labombarda
Florencia
F
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires, Argentina.
González
Susana L
SL
Lima
Analia
A
Roig
Paulina
P
Guennoun
Rachida
R
Schumacher
Michael
M
de Nicola
Alejandro F
AF
D053687:Adult Stem Cells / Q000187:drug effects*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects*; D009919:Orchiectomy / Q000379:methods; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D011372:Progestins / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D011374:Progesterone; D011372:Progestins; D012333:RNA, Messenger; D014157:Transcription Factors; D029961:Zebrafish Proteins; C571328:Mog protein, rat; C000715628:Nkx2-2 protein, rat; C498633:Olig1 protein, rat; C489071:Plp1 protein, rat; C000715630:nkx2.2b protein, zebrafish