Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration

DE NICOLA A; LABOMBARDA F; GONZALEZ DENISELLE, C; GONZALEZ S; GARAY L; MAYER M; GARGIULO G; GUENNOUN R; SCHUMACHER M

Frontiers in Neuroendocrinology

Elsevier

Año: 2009 p. 173 - 187

0091-3022

Studies on the neuroprotective and promyelinating effects of progesterone in the nervous system are ofgreat interest due to their potential clinical connotations. In peripheral neuropathies, progesterone andreduced derivatives promote remyelination, axonal regeneration and the recovery of function. In traumaticbrain injury (TBI), progesterone has the ability to reduce edema and inflammatory cytokines, preventneuronal loss and improve functional outcomes. Clinical trials have shown that short-and long-termprogesterone treatment induces a significant improvement in the level of disability among patients withbrain injury. In experimental spinal cord injury (SCI), molecular markers of functional motoneuronsbecome impaired, including brain-derived neurotrophic factor (BDNF) mRNA, Na,K-ATPase mRNA, microtubule-associated protein 2 and choline acetyltransferase (ChAT). SCI also produces motoneuron chromatolysis.Progesterone treatment restores the expression of these molecules while chromatolysis subsided.SCI also causes oligodendrocyte loss and demyelination. In this case, a short progesterone treatmentenhances proliferation and differentiation of oligodendrocyte progenitors into mature myelin-producingcells, whereas prolonged treatment increases a transcription factor (Olig1) needed to repair injuryinduceddemyelination. Progesterone neuroprotection has also been shown in motoneuron neurodegeneration.In Wobbler mice spinal cord, progesterone reverses the impaired expression of BDNF, ChAT andNa,K-ATPase, prevents vacuolar motoneuron degeneration and the development of mitochondrial abnormalities,while functionally increases muscle strength and the survival of Wobbler mice. Multiple mechanismscontribute to these progesterone effects, and the role played by classical nuclear receptors, extranuclear receptors, membrane receptors, and the reduced metabolites of progesterone in neuroprotectionand myelin formation remain an exciting field worth of exploration