title: Progesterone treatment reduces NADPH-diaphorase/nitric oxide synthase in Wobbler mouse motoneuron disease.
abstract: Previous work demonstrated that progesterone (PROG) treatment attenuates morphological, molecular and functional abnormalities in the spinal cord of the Wobbler (Wr) mouse, a genetic model of motoneuron degeneration. Wr mice show a marked up-regulation of the nitric oxide synthesizing enzyme (NOS). Since nitric oxide is a highly reactive species, it may play a role in neuropathology of Wr mice. We now studied if PROG neuroprotection involved changes of NOS activity in motoneurons and astrocytes, determined by the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHD) histochemical reaction. Two and four-month-old Wr mice at the progressive and stabilization stages of the disease, respectively, and their age-matched controls were left untreated or received a single 20-mg PROG pellet for 18 days. PROG reduced the high number of NADPHD-active motoneurons and white matter astrocytes in 2-month-old Wr mice but was unable to change the low number of NADPHD-active motoneurons in 4-month-old Wr mice or astrocytes in this age group. A large number of motoneurons in 2-month-old Wr mice showed a vacuolated phenotype, which was significantly reverted by PROG treatment. In summary, PROG treatment during the early symptomatic stage of the disease caused a significant reduction of NADPHD-active motoneurons and astrocytes and also reduced vacuolated degenerating cells, suggesting that blockade of NO synthesis and oxidative damage may contribute to steroid neuroprotection.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, University of Buenos Aires, Argentina.
authors.forename: María Claudia
authors.initials: MC
authors.lastname: González Deniselle
authors.forename: Laura
authors.initials: L
authors.lastname: Garay
authors.forename: Juan José
authors.initials: JJ
authors.lastname: López-Costa
authors.forename: Susana
authors.initials: S
authors.lastname: González
authors.forename: Analía
authors.initials: A
authors.lastname: Mougel
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: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology; D002452:Cell Count; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D011374:Progesterone; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase