Progesterone treatment reduces NADPH-diaphorase/nitirc oxide synthase in Wobbler mouse motoneuron disease

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

BRAIN RESEARCH

Elsevier

Lugar: London; Año: 2004 vol. 1014 p. 71 - 79

0006-8993

Previous work demonstrated that progesterone (PROG) treatment attenuates morphological, molecular and functional abnormalities in the spinal cord of theWobbler (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 ofWr 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-oldWr mice but was unable to change the low number of NADPHD-active motoneurons in 4-month-oldWr mice or astrocytes in this age group. A large number of motoneurons in 2-month-oldWr 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.