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

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)....

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Detalles Bibliográficos
Autores principales: González Deniselle, M.C., Garay, L., López-Costa, J.J., González, S., Mougel, A., Guennoun, R., Schumacher, M., De Nicola, A.F.
Formato: JOUR
Materias:
Endocrine and autonomic regulation
Motoneuron disease
Neuroendocrine regulation: other
Neuroprotection
Nitric oxide synthase
Progesterone
Wobbler mouse
3alpha hydroxy 5alpha pregnan 20 one
5alpha pregnane 3,20 dione
methylprednisolone
nitric oxide synthase
progesterone
reduced nicotinamide adenine dinucleotide phosphate dehydrogenase
animal model
animal tissue
article
astrocyte
cell vacuole
controlled study
disease course
drug blood level
drug effect
drug potency
enzyme activity
female
histochemistry
male
motoneuron
motor neuron disease
mouse
neuroprotection
nonhuman
phenotype
priority journal
white matter
Animals
Astrocytes
Cell Count
Down-Regulation
Female
Male
Mice
Mice, Neurologic Mutants
Motor Neuron Disease
Motor Neurons
NADPH Dehydrogenase
Nitric Oxide Synthase
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00068993_v1014_n1-2_p71_GonzalezDeniselle
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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. © 2004 Elsevier B.V. All rights reserved.

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