INVESTIGADORES
GARGIULO MONACHELLI Gisella Mariana
artículos
Título:
Stage dependent effects of progesterone on motoneurons and glial cells of Wobbler mouse spinal cord degeneration
Autor/es:
MEYER M; GONZALEZ DENISELLE M.C; GARAY L; GARGIULO MONACHELLI GM; LIMA A,; ROIG P; GUENNOUN R,; SCHUMACHER M,; DE NICOLA AF.
Revista:
CELLULAR AND MOLECULAR NEUROBIOLOGY.
Editorial:
Springer US
Referencias:
Año: 2010 vol. 30 p. 123 - 135
ISSN:
0272-4340
Resumen:
In the Wobbler mouse, a mutation in the Vps54 gene is accompanied by
motoneuron degeneration and astrogliosis in the cervical spinal cord. Previous work
has shown that these abnormalities are greatly attenuated by progesterone treatment
of clinically aflicted Wobblers. However, whether progesterone is effective at all
disease stages has not yet been tested. The present work used genotyped (wr/wr)
Wobbler mice at three periods of the disease: early progressive (1-2 months),
established (5-8 months) or late stages (12 months) and age-matched wildtype controls
(NFR/NFR), half of which were implanted with a progesterone pellet (20 mg) for 18
days. In untreated Wobblers, degenerating vacuolated motoneurons were initially
abundant, experienced a slight reduction at the established stage and dramatically
diminished during the late period. In motoneurons, the cholinergic marker choline
acetyltransferase (ChaT) was reduced at all stages of the Wobbler disease, whereas
hyperexpression of the growth-associated protein (GAP43) mRNA preferentially
occurred at the early progressive and established stages. Progesterone therapy
significantly reduced motoneuron vacuolation, enhanced ChAT immunoreactive
perikarya and reduced the hyperexpression of GAP43 during the early progressive and
established stages. At all stage periods, untreated Wobblers showed high density of
glial fibrillary acidic protein (GFAP) + astrocytes and decreased number of glutamine
synthase (GS) immunostained cells. Progesterone treatment down-regulated GFAP+
astrocytes and up-regulated GS+ cell number. These data reinforced the usefulness of
progesterone to improve motoneuron and glial cell abnormalities of Wobbler mice and
further showed that therapeutic benefit seems more effective at the early progressive
and established periods, rather than on advance stages of spinal cord
neurodegeneration.