title: A functional progesterone receptor is required for immunomodulation, reduction of reactive gliosis and survival of oligodendrocyte precursors in the injured spinal cord.
abstract: The anti-inflammatory effects of progesterone have been increasingly recognized in several neuropathological models, including spinal cord inflammation. In the present investigation, we explored the regulation of proinflammatory factors and enzymes by progesterone at several time points after spinal cord injury (SCI) in male rats. We also demonstrated the role of the progesterone receptor (PR) in inhibiting inflammation and reactive gliosis, and in enhancing the survival of oligodendrocyte progenitors cells (OPC) in injured PR knockout (PRKO) mice receiving progesterone. First, after SCI in rats, progesterone greatly attenuated the injury-induced hyperexpression of the mRNAs of interleukin 1β (IL1β), IL6, tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), all involved in oligodendrocyte damage. Second, the role of the PR was investigated in PRKO mice after SCI, in which progesterone failed to reduce the high expression of IL1β, IL6, TNFα and IκB-α mRNAs, the latter being considered an index of reduced NF-κB transactivation. These effects occurred in a time framework coincident with a reduction in the astrocyte and microglial responses. In contrast to wild-type mice, progesterone did not increase the density of OPC and did not prevent apoptotic death of these cells in PRKO mice. Our results support a role of PR in: (a) the anti-inflammatory effects of progesterone; (b) the modulation of astrocyte and microglial responses and (c) the prevention of OPC apoptosis, a mechanism that would enhance the commitment of progenitors to the remyelination pathway in the injured spinal cord.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Labombarda
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Jure
authors.affiliation: Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina; Laboratory of Nociception and Neuropathic Pain, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: Analia
authors.initials: A
authors.lastname: Lima
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: Paulina
authors.initials: P
authors.lastname: Roig
authors.affiliation: U1195 Inserm and Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
authors.forename: Rachida
authors.initials: R
authors.lastname: Guennoun
authors.affiliation: U1195 Inserm and Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Schumacher
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina. Electronic address: alejandrodenicola@gmail.com.
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000235:genetics; D005911:Gliosis / Q000276:immunology / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000235:genetics / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000276:immunology / Q000473:pathology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011980:Receptors, Progesterone
keywords: Astrocytes; Knockout mice; Microglia; Neuroinflammation; Progesterone receptor; Spinal cord injury