Basis of progesterone protection in spinal cord neurodegeneration

GONZALEZ DENISELLE, MC; LOPEZ COSTA, J.J; GONZÁLEZ S.L; GARAY L; GUENNOUN R; SCHUMACHER M; DE NICOLA A. F.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2003 vol. 83 p. 199 - 209

0960-0760

Progesterone neuroprotection has been reported in experimental brain, peripheral nerve and spinal cord injury. To investigate for a similar role in neurodegeneration, we studied progesterone effects in theWobbler mouse, amutant presenting severe motoneuron degeneration and astrogliosis of the spinal cord. Implant of a single progesterone pellet (20 mg) during 15 days produced substantial changes inWobbler mice spinal cord. Morphologically, motoneurons of untreated Wobbler mice showed severe vacuolation of intracellular organelles including mitochondria. In contrast, neuropathology was less pronounced in Wobbler mice receiving progesterone, together with a reduction ofvacuolated cells and preservation of mitochondrial ultrastructure. Determination of mRNAs for the 3 and 1 subunits of neuronal Na, K-ATPase, showed thatmRNAlevels in untreated mice were significantly reduced, whereas progesterone therapy re-established the expressionof both subunits. Additionally, progesterone treatment of Wobbler mice attenuated the aberrant expression of the growth-associated protein (GAP-43) mRNA which otherwise occurred in motoneurons of untreated animals. The hormone, however, was without effecton astrocytosis of Wobbler mice, determined by glial fibrillary acidic protein (GFAP)-immunostaining. Lastly, progesterone treatment of Wobbler mice enhanced grip strength and prolonged survival at the end of the 15-day observation period. Recovery of morphology and molecular motoneuron parameters of Wobbler mice receiving progesterone, suggest a new and important role for this hormone in theprevention of spinal cord neurodegenerative disorders.