title: Experimental and clinical evidence for the protective role of progesterone in motoneuron degeneration and neuroinflammation.
abstract: Far beyond its role in reproduction, progesterone exerts neuro-protective, promyelinating, and anti-inflammatory effects in the nervous system. These effects are amplified under pathological conditions, implying that changes of the local environment sensitize 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 the effects of progesterone in mice with induced experimental autoimmune encephalomyelitis (EAE), a commonly used model of multiple sclerosis. In EAE mice, progesterone attenuates the clinical severity, decreases demyelination and neuronal dysfunction, increases axonal counts, reduces the formation of amyloid precursor protein profiles, and decreases the aberrant expression of growth-associated proteins. These actions of progesterone may be due to multiple mechanisms, considering that classic nuclear receptors, extranuclear receptors, and membrane receptors are all expressed in the spinal cord. Although many aspects of progesterone action in humans remain unsolved, data provided by experimental models makes getting to this objective closer than previously expected.
authors.forename: M C
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.forename: L
authors.initials: L
authors.lastname: Garay
authors.forename: M
authors.initials: M
authors.lastname: Meyer
authors.forename: G
authors.initials: G
authors.lastname: Gargiulo-Monachelli
authors.forename: F
authors.initials: F
authors.lastname: Labombarda
authors.forename: S
authors.initials: S
authors.lastname: Gonzalez
authors.forename: R
authors.initials: R
authors.lastname: Guennoun
authors.forename: M
authors.initials: M
authors.lastname: Schumacher
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola