INVESTIGADORES
GARGIULO MONACHELLI Gisella Mariana
artículos
Título:
Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration
Autor/es:
DE NICOLA AF; LABOMBARDA F; DENISELLE MC; GONZALEZ SL; GARAY L,; MEYER M,; GARGIULO MONACHELLI G,; GUENNOUN R,; SCHUMACHER M,
Revista:
FRONTIERS IN NEUROENDOCRINOLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2009 vol. 30 p. 173 - 187
ISSN:
0091-3022
Resumen:
Studies on the neuroprotective and promyelinating effects of progesterone in the nervous system are of
great interest due to their potential clinical connotations. In peripheral neuropathies, progesterone and
reduced derivatives promote remyelination, axonal regeneration and the recovery of function. In traumatic
brain injury (TBI), progesterone has the ability to reduce edema and inflammatory cytokines, prevent
neuronal loss and improve functional outcomes. Clinical trials have shown that short-and long-term
progesterone treatment induces a significant improvement in the level of disability among patients with
brain injury. In experimental spinal cord injury (SCI), molecular markers of functional motoneurons
become 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 treatment
enhances proliferation and differentiation of oligodendrocyte progenitors into mature myelin-producing
cells, whereas prolonged treatment increases a transcription factor (Olig1) needed to repair injuryinduced
demyelination. Progesterone neuroprotection has also been shown in motoneuron neurodegeneration.
In Wobbler mice spinal cord, progesterone reverses the impaired expression of BDNF, ChAT and
Na,K-ATPase, prevents vacuolar motoneuron degeneration and the development of mitochondrial abnormalities,
while functionally increases muscle strength and the survival of Wobbler mice. Multiple mechanisms
contribute to these progesterone effects, and the role played by classical nuclear receptors, extra
nuclear receptors, membrane receptors, and the reduced metabolites of progesterone in neuroprotection
and myelin formation remain an exciting field worth of exploration.