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Artículo

The Progesterone receptor agonist Nestorone holds back proinflammatory mediators and neuropathology in Wobbler Mouse motoneuron degeneration

Meyer, MariaIcon ; Gonzalez Deniselle, Maria ClaudiaIcon ; Garay, Laura InesIcon ; Sitruk Ware, Regine; Guennoun, Rachida; de Nicola, Alejandro FedericoIcon
Fecha de publicación: 12/11/2015
Editorial: Elsevier
Revista: Neuroscience
ISSN: 0306-4522
e-ISSN: 1873-7544
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Wobbler mutant mice suffer from progressive motoneuron degeneration and glial cell reactivity in the spinal cord. To prevent development of these abnormalities, we employed Nestorone, a high-affinity progesterone receptor agonist endowed with neuroprotective, promyelinating and anti-inflammatory activities in experimental brain ischemia, preventing neuroinflammation and chemical degeneration. Five-month-old Wobbler mice (wr-/wr-) received s.c. injections of 200μg/day/mouse of Nestorone in vegetable oil or vehicle for 10days. Control NFR/NFR mice (background strain for Wobbler) received vehicle only. Vehicle-treated Wobblers showed typical spinal cord abnormalities, such as vacuolated motoneurons, decreased immunoreactive choline-acetyltransferase, decreased expression of glutamine synthase (GS), increased glial fibrillary acidic protein-positive (GFAP) astrogliosis and curved digits in forelimbs. These cell-specific abnormalities were normalized in Nestorone-treated Wobblers. In addition, vehicle-treated Wobblers showed Iba1+ microgliosis, high expression of the microglial marker CD11b mRNA and up-regulation of the proinflammatory markers TNFα and iNOS mRNAs. In Nestorone-treated Wobblers, Iba1+ microgliosis subsided, whereas CD11b, TNFα and iNOS mRNAs were down-regulated. NFκB mRNA was increased in Wobbler spinal cord and decreased by Nestorone, whereas expression of its inhibitor IκBα was increased in Nestorone-treated Wobblers compared to control mice and vehicle-treated Wobblers. In conclusion, our results showed that Nestorone restraining effects on proinflammatory mediators, microgliosis and astrogliosis may support neurons in their resistance against degenerative processes
Palabras clave: Wobbler , Progesterone , Spinal Cord , Gliosis , Astrocytes
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/23052
URL: http://www.sciencedirect.com/science/article/pii/S0306452215008179
DOI: http://dx.doi.org/10.1016/j.neuroscience.2015.09.007
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Meyer, Maria; Gonzalez Deniselle, Maria Claudia; Garay, Laura Ines; Sitruk Ware, Regine; Guennoun, Rachida; et al.; The Progesterone receptor agonist Nestorone holds back proinflammatory mediators and neuropathology in Wobbler Mouse motoneuron degeneration; Elsevier; Neuroscience; 308; 12-11-2015; 51-63
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