Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord

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...

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Autores principales:	Garay, L., Tüngler, V., Deniselle, M.C.G., Lima, A., Roig, P., De Nicola, A.F.
Formato:	JOUR
Materias:	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 Spinal Cord
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_03064522_v192_n_p588_Garay
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_03064522_v192_n_p588_Garay2023-10-03T15:22:24Z Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord Garay, L. Tüngler, V. Deniselle, M.C.G. Lima, A. Roig, P. De Nicola, A.F. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03064522_v192_n_p588_Garay
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Garay, L. Tüngler, V. Deniselle, M.C.G. Lima, A. Roig, P. De Nicola, A.F.
author_facet	Garay, L. Tüngler, V. Deniselle, M.C.G. Lima, A. Roig, P. De Nicola, A.F.
author_sort	Garay, L.
title	Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
title_short	Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
title_full	Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
title_fullStr	Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
title_full_unstemmed	Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
title_sort	progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord
url	http://hdl.handle.net/20.500.12110/paper_03064522_v192_n_p588_Garay
work_keys_str_mv	AT garayl progesteroneattenuatesdemyelinationandmicroglialreactioninthelysolecithininjuredspinalcord AT tunglerv progesteroneattenuatesdemyelinationandmicroglialreactioninthelysolecithininjuredspinalcord AT denisellemcg progesteroneattenuatesdemyelinationandmicroglialreactioninthelysolecithininjuredspinalcord AT limaa progesteroneattenuatesdemyelinationandmicroglialreactioninthelysolecithininjuredspinalcord AT roigp progesteroneattenuatesdemyelinationandmicroglialreactioninthelysolecithininjuredspinalcord AT denicolaaf progesteroneattenuatesdemyelinationandmicroglialreactioninthelysolecithininjuredspinalcord
_version_	1782028050759680000

Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord

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