Experimental and Clinical evidence for the protective role Of progesterone in motoneurone degeneration and neuroinflammation

GONZALEZ DENISELLE MC; GARAY, L. I.; MEYER, M; GARGIULO MONACHELLI GISELLA; LABOMBARDA F; GONZALEZ SL; GUENNOUN, R.; SCHUMMACHER M; DE NICOLA A. F.

. Hormone Molecular Biology and Clinical Investigation

De Gruyter

Año: 2011 p. 1 - 15

1868-1891

Far beyond its role in reproduction, progesterone exerts neuroprotective, promyelinating and anti-inflammatory effects in the nervous system. These effects are amplified under pathological conditions, implying that changes of the local environment sensitize the nervous tissues to steroid therapy. The present survey covers our results of progesterone neuroprotection in a motoneuron neurodegeneration model and a neuroinflammation model. In the degenerating spinal cord of the Wobbler mouse, progesterone reverses the impaired expression of neurotrophins, increases enzymes of neurotransmission and metabolism, prevents oxidative damage of motoneurons and their vacuolar degeneration (paraptosis), and attenuates the development of mitochondrial abnormalities. After long-term treatment, progesterone also increases muscle strength and the survival of Wobbler mice. Subsequently, this review describes progesterone effects in mice with induced experimental autoimmune encephalomyelitis (EAE), a commonly used model of multiple sclerosis (MS). In EAE mice, progesterone attenuates the clinical severity, decreases demyelination and neuronal dysfunction, increases axonal counts, reduces the formation of amyloid precursor protein (APP) profiles, and decreases the aberrant expression of growth-associated proteins. These actions of progesterone may be due to multiple mechanisms, considering that classical nuclear receptors, extranuclear receptors and membrane receptors are all expressed in the spinal cord. In spite of the fact that many aspects of progesterone action in humans remains unsolved, data provided by experimental models makes this objective getting closer than previously expected.