INVESTIGADORES
DE NICOLA Alejandro Federico
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 G, GUENNOUN R, SCHUMACHER M.
Revista:
FRONTIERS IN NEUROENDOCRINOLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Lugar: Holanda; Año: 2009 vol. 30 p. 173 - 187
ISSN:
0091-3022
Resumen:
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Studies on the neuroprotective and
promyelinating effects of progesterone in the nervous system are rapidly
expanding due to their potential clinical connotations. In peripheral
neuropathies, progesterone and reduced derivatives promote remyelination,
axonal regeneration and the recovery of function. In experimental brain trauma,
progesterone has the ability to reduce edema and inflammatory cytokines,
prevent neuronal loss and improve functional outcomes. A recent clinical trial (ProTECT)
has shown a significant improvement in the level of disability among patients
with moderate brain injury. Experimental spinal cord injury impairs molecular
markers of functional motoneurons, including brain-derived neurotrophic factor (BDNF)
mRNA, Na,K-ATPase mRNA, microtubule-associated protein 2 and choline
acetyltransferase (ChAT) and induces motoneuron chromatolysis. Progesterone
restores the expression levels of these molecules while chromatolysis subsided.
Spinal cord injury 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 the transcription factors needed to repair injury-induced
demyelination. Progesterone neuroprotection has also been demonstrated in a
motoneuron neurodegeneration model. In the Wobbler mouse spinal cord,
progesterone reverses the impaired expression of BDNF, ChAT and Na,K-ATPase,
prevents vacuolar motoneuron degeneration (paraptosis) and the development of
mitochondrial abnormalities, while functionally increases muscle strength and
the survival of Wobbler mice. Multiple mechanisms may explain these actions of
progesterone. However, the specific role play by classical nuclear receptors,
extranuclear receptors, membrane receptors, and the dihydro and tetrahydro
metabolites of progesterone in neuroprotection and myelin formation remain an
exciting field worth of exploration.
