INVESTIGADORES
DE NICOLA Alejandro Federico
artículos
Título:
The progesterone receptor agonist Nestorone holds back proinflammatory mediators and neuropathology in the wobbler mouse model of motoneuron degeneration
Autor/es:
MEYER M.; GONZALEZ DENISELLE, MARÍA CLAUDIA; LAURA GARAY; SITRUK-WARE R; GUENNOUN R; SCHUMACHER M; DE NICOLA A.F.
Revista:
NEUROSCIENCE
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2015 vol. 308 p. 51 - 63
ISSN:
0306-4522
Resumen:
Wobbler mutant mice suffer from progressive motoneurondegeneration and glial cell reactivity in the spinal cord. To prevent developmentof these abnormalities, we employed Nestorone, a high affinity progesteronereceptor agonist endowed with neuroprotective, promyelinating andanti-inflammatory activities in experimental brain ischemia, preventing neuroinflammationand chemical degeneration. Five month old Wobbler mice (wr -/ wr-) received s.c. injections of200 mg /day /mouse of Nestorone in vegetable oil or vehicle for 10 days. ControlNFR/NFR mice (background strain for Wobbler) received vehicle only.Vehicle-treated Wobblers showed typical spinal cord abnormalities, such as vacuolatedmotoneurons, decreased immunoreactive choline-acetyltransferase, decreased expressionof glutamine synthase, increased glial fibrillary acidic protein positive(GFAP) astrogliosis and curved digits in forelimbs. These cell-specific abnormalitieswere normalized in Nestorone treated Wobblers. In addition, vehicle-treated Wobblersshowed Iba1+ microgliosis, high expression of the microglial marker CD11b mRNAand up-regulation of the proinflammatory markers TNFa and iNOS mRNAs. In Nestorone-treated Wobblers, Iba1+ microgliosissubsided, whereas CD11b, TNFa and iNOS mRNAs were down-regulated. NFkB mRNA was increased in Wobbler spinal cord and decreased by Nestorone,whereas expression of its inhibitor IkBa was increased in Nestorone-treated Wobblers compared to controlmice and vehicle-treated Wobblers. In conclusion, our results showed thatNestorone restraining effects on proinflammatory mediators, microgliosis and astrogliosismay support neurons in their resistance against degenerative processes.
