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Abstract:

Progesterone treatment of mice with experimental autoimmune encephalomyelitis has shown beneficial effects in the spinal cord according to enhanced clinical, myelin and neuronal-related parameters. In the present work, we report progesterone effects in a model of primary demyelination induced by the intraspinal injection of lysophospatidylcholine (LPC). C57Bl6 adult male mice remained steroid-untreated or received a single 100 mg progesterone implant, which increased circulating steroid levels to those of mouse pregnancy. Seven days afterwards mice received a single injection of 1% LPC into the dorsal funiculus of the spinal cord. A week after, anesthetized mice were perfused and paraffin embedded sections of the spinal cord stained for total myelin using Luxol Fast Blue (LFB) histochemistry, for myelin basic protein (MBP) immunohistochemistry and for determination of OX-42+ microglia/macrophages. Cryostat sections were also prepared and stained for oligodendrocyte precursors (NG2+ cells) and mature oligodendrocytes (CC1+ cells). A third batch of spinal cords was prepared for analysis of the microglial marker CD11b mRNA using qPCR. Results showed that progesterone pretreatment of LPC-injected mice decreased by 50% the area of demyelination, evaluated by either LFB staining or MBP immunostaining, increased the density of NG2+ cells and of mature, CC1+ oligodendrocytes and decreased the number of OX-42+ cells, respect of steroid-untreated LPC mice. CD11b mRNA was hyperexpressed in LPC-treated mice, but significantly reduced in LPC-mice receiving progesterone. These results indicated that progesterone antagonized LPC injury, an effect involving (a) increased myelination; (b) stimulation of oligodendrocyte precursors and mature oligodendrocytes, and (c) attenuation of the microglial/macrophage response. Thus, use of a focal demyelination model suggests that progesterone exerts promyelinating and anti-inflammatory effects at the spinal cord level. © 2011 IBRO.

Registro:

Documento: Artículo
Título:Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
Autor:Garay, L.; Tüngler, V.; Deniselle, M.C.G.; Lima, A.; Roig, P.; De Nicola, A.F.
Filiación:Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Obligado 2490, 1428 Buenos Aires, Argentina
Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Paraguay 2155, 1425 Buenos Aires, Argentina
Institut für Pharmakologie und Toxikologie, Charité - Universitätsmedizin Berlin, Dorotheenstr. 94, 10117 Berlin, Germany
Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
Palabras clave:Demyelination; Lysolecithin; Microglial reaction; Progesterone; Remyelination; CD11b antigen; lysophosphatidylcholine; messenger RNA; myelin basic protein; progesterone; animal experiment; animal model; animal tissue; antiinflammatory activity; article; cell density; controlled study; demyelination; dorsal root; drug effect; drug implant; macrophage; male; microglia; mouse; myelination; neural stem cell; nonhuman; oligodendroglia; priority journal; single drug dose; spinal cord injury; Animals; Demyelinating Diseases; Disease Models, Animal; Immunohistochemistry; Lysophosphatidylcholines; Male; Mice; Mice, Inbred C57BL; Microglia; Progesterone; Spinal Cord
Año:2011
Volumen:192
Página de inicio:588
Página de fin:597
DOI: http://dx.doi.org/10.1016/j.neuroscience.2011.06.065
Título revista:Neuroscience
Título revista abreviado:Neuroscience
ISSN:03064522
CODEN:NRSCD
CAS:lysophosphatidylcholine, 93794-93-5; progesterone, 57-83-0; Lysophosphatidylcholines; Progesterone, 57-83-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v192_n_p588_Garay

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Citas:

---------- APA ----------
Garay, L., Tüngler, V., Deniselle, M.C.G., Lima, A., Roig, P. & De Nicola, A.F. (2011) . Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord. Neuroscience, 192, 588-597.
http://dx.doi.org/10.1016/j.neuroscience.2011.06.065
---------- CHICAGO ----------
Garay, L., Tüngler, V., Deniselle, M.C.G., Lima, A., Roig, P., De Nicola, A.F. "Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord" . Neuroscience 192 (2011) : 588-597.
http://dx.doi.org/10.1016/j.neuroscience.2011.06.065
---------- MLA ----------
Garay, L., Tüngler, V., Deniselle, M.C.G., Lima, A., Roig, P., De Nicola, A.F. "Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord" . Neuroscience, vol. 192, 2011, pp. 588-597.
http://dx.doi.org/10.1016/j.neuroscience.2011.06.065
---------- VANCOUVER ----------
Garay, L., Tüngler, V., Deniselle, M.C.G., Lima, A., Roig, P., De Nicola, A.F. Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord. Neuroscience. 2011;192:588-597.
http://dx.doi.org/10.1016/j.neuroscience.2011.06.065