IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Progesterone effects on neuronal brain-derived neurotrophic factor and glial cells during progression of Wobbler mouse neurodegeneration.
Autor/es:
MEYER M; GONZÁLEZ DENISELLE M.C; GARGIULO MONACHELLI, G.M; GARAY L; SCHUMMACHER M; GUENNOUN, R.; DE NICOLA A. F.
Revista:
NEUROSCIENCE
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2011 p. 267 - 279
ISSN:
0306-4522
Resumen:
Motoneurons from symptomatic (SYM) 5-8 months old Wobbler mice show depletion ofneurotrophin brain-derived neurotrophic factor (BDNF) mRNA, while progesterone treatment ofWobblers revert this depletion. We now compared progesterone regulation of BDNF in motoneurons and oligodendrocytes at the progressive (EP, 1-3 months), SYM and late stages (LS, 12-13 months) of Wobbler and control NFR/NFR mice. To this end, controls and Wobblers at different stages were subdivided into steroid-untreated and progesterone-treated groups, the last one receiving a 20 mg progesterone pellet during 18 days. BDNF mRNA was determined in the ventral, intermediolateral and dorsal gray matter using film autoradiography and in motoneurons using a grain counting procedure.BDNF mRNA was already depleted at the EP stage of Wobblers, but progesterone was inactive at this period. In contrast, the low levels of BDNF mRNA in SYM Wobblers were re-established by  progesterone in the three gray matter regions analyzed. Progesterone also increased BDNF mRNA in LS Wobblers, according to grain counting procedures. However, BDNF protein content analyzed by ELISA in ventral horns or immunostaining of motoneurons, was normal in steroid-naïve SYM Wobblers but decreased by progesterone, suggesting increased anterograde transport and /or release of neuronal BDNF. Wobbler mice also showed depletion of CC1 immunopositive oligodendrocytes, and progesterone treatment enhanced the density of BDNF+ and CC1+ oligodendrocytes in EP, SYM and LS Wobblers. Our results suggest that BDNF could mediate progesterone effects on motoneurons at the SYM and LS periods, whereas effects on oligodendrocytes occurred at all stages of the Wobbler disease. We hypothesize that these progesterone effects are neuroprotective and promote myelination in spinal cord motoneurodegeneration.