The progesterone receptor agonist Nestorone holds back proinflammatory mediators and neuropathology in the wobbler mouse model of motoneuron degeneration

Neuroscience
Maria MeyerA F De Nicola

Abstract

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 C...Continue Reading

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Citations

Jun 25, 2016·Journal of Molecular Endocrinology·Silvia GiattiMarzia Pesaresi
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Jan 28, 2021·International Journal of Molecular Sciences·Hilal CihankayaVeronika Matschke
Jun 18, 2021·Cellular and Molecular Neurobiology·Alejandro F De NicolaMaria Claudia Gonzalez Deniselle

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