title: Basis of progesterone protection in spinal cord neurodegeneration.
abstract: 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 the Wobbler mouse, a mutant presenting severe motoneuron degeneration and astrogliosis of the spinal cord. Implant of a single progesterone pellet (20 mg) during 15 days produced substantial changes in Wobbler 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 of vacuolated cells and preservation of mitochondrial ultrastructure. Determination of mRNAs for the alpha 3 and beta 1 subunits of neuronal Na, K-ATPase, showed that mRNA levels in untreated mice were significantly reduced, whereas progesterone therapy re-established the expression of 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 effect on 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 the prevention of spinal cord neurodegenerative disorders.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Department of Human Biochemistry, Faculty of Medicine, Instituto de Biologia y Medicina Experimental, University of Buenos Aires, Obligado 2490, 1428 Buenos Aires, Argentina.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lopez Costa
authors.forename: Susana L
authors.initials: SL
authors.lastname: Gonzalez
authors.forename: Florencia
authors.initials: F
authors.lastname: Labombarda
authors.forename: Laura
authors.initials: L
authors.lastname: Garay
authors.forename: Rachida
authors.initials: R
authors.lastname: Guennoun
authors.forename: Michael
authors.initials: M
authors.lastname: Schumacher
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D027682:Cation Transport Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D019922:GAP-43 Protein / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008854:Microscopy, Electron; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*
chemical_list: D027682:Cation Transport Proteins; D002843:Chromatin; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D011374:Progesterone; D000251:Adenosine Triphosphatases; C022761:potassium transporting ATPase