PROGESTERONE RESTORES RETROGRADE LABELLING OF CERVICAL MOTONEURONS IN WOBBLER MOUSE MOTONEURON DISEASE

GONZALEZ DENISELLE M.C.; GARAY L.; GONZALEZ S.; GUENNOUN R.; SCHUMACHER M; DE NICOLA A.F.

EXPERIMENTAL NEUROLOGY

Elsevier

Lugar: Holanda; Año: 2005 vol. 195 p. 518 - 523

0014-4886

The Wobbler mouse, a genetic mutant characterized by neurodegeneration of the cervical spinal cord, has been used to test the efficacy of novel treatments for human motoneuron diseases (HMD). Previous reports have shown that slow axonal transport is impaired in Wobbler mice and other models of HMD. Since progesterone (PROG) corrects morphological, molecular and functional abnormalities of Wobbler mice, we studied if steroid exposure for 8 weeks restored retrograde axonal transport by measuring motoneuron labelling with fluorogold after injection of the dye into the limb muscles. Fluorogold was injected into forelimb biceps bracchii and flexor muscles or into the rearlimb gastrocnemius muscle; 6 days latter fluorescent motoneurons were counted in the cervical (C5-T1) or lumbar (L3-L5) spinal cord regions.  A pronounced reduction ( - 42.2 %) of the number of fluorescent motoneurons in Wobbler mice cervical cord was determined, which was significantly corrected after PROG treatment. In contrast, labelling of lumbar motoneurons was unchanged in untreated or treated Wobbler mice respect of controls. In no case PROG showed an effect in control mice. Concomitantly, PROG slightly but significantly restored biceps weight in Wobbler mice. We postulate a dual role for PROG in the Wobbler mouse, in part by prevention of  motoneuron degeneration, and secondarily by enhancement of axonal transport. Functionally, the latter mechanism could improve the traffic of neurotrophic factors from the forelimb muscles into the ailing motoneurons of murine models of HMD.