Experimental and clinical evidence for the protective role of progesterone in motoneuron degeneration and neuroinflammation

GONZÁLEZ DENISELLE MC; GARAY L; MEYER M; GARGIULO-MONACHELLI GM; LABOMBARDA F; GONZALEZ S; GUENNOUN R; SCHUMACHER M; DE NICOLA AF

Hormone molecular biology and clinical investigation (Horm Mol Biol Clin Investig)

De Gruyter

Año: 2011 p. 403 - 411

1868-1891

Far beyond its role in reproduction, progesterone exertsneuro protective, promyelinating, and anti-infl ammatoryeffects in the nervous system. These effects are amplifi edunder pathological conditions, implying that changes of thelocal environment sensitize nervous tissues to steroid therapy.The present survey covers our results of progesterone neuroprotectionin a motoneuron neurodegeneration model anda neuroinfl ammation model. In the degenerating spinal cordof the Wobbler mouse, progesterone reverses the impairedexpression of neurotrophins, increases enzymes of neurotransmissionand metabolism, prevents oxidative damage ofmotoneurons and their vacuolar degeneration (paraptosis), andattenuates the development of mitochondrial abnormalities.After long-term treatment, progesterone also increases musclestrength and the survival of Wobbler mice. Subsequently,this review describes the effects of progesterone in mice withinduced experimental autoimmune encephalomyelitis (EAE),a commonly used model of multiple sclerosis. In EAE mice,progesterone attenuates the clinical severity, decreases demyelinationand neuronal dysfunction, increases axonal counts,reduces the formation of amyloid precursor protein profi les,and decreases the aberrant expression of growth-associatedproteins. These actions of progesterone may be due tomultiple mechanisms, considering that classic nuclear receptors,extranuclear receptors, and membrane receptors are allexpressed in the spinal cord. Although many aspects of progesteroneaction in humans remain unsolved, data providedby experimental models makes getting to this objective closerthan previously expected.