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Publication : Progesterone treatment reduces NADPH-diaphorase/nitric oxide synthase in Wobbler mouse motoneuron disease.

First Author  González Deniselle MC Year  2004
Journal  Brain Res Volume  1014
Issue  1-2 Pages  71-9
PubMed ID  15212993 Mgi Jnum  J:90944
Mgi Id  MGI:3045550 Doi  10.1016/j.brainres.2004.04.004
Citation  Gonzalez Deniselle MC, et al. (2004) Progesterone treatment reduces NADPH-diaphorase/nitric oxide synthase in Wobbler mouse motoneuron disease. Brain Res 1014(1-2):71-9
abstractText  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.
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