Article

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

Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, University of Buenos Aires, Argentina.
Brain Research (impact factor: 2.73). 08/2004; 1014(1-2):71-9. DOI:10.1016/j.brainres.2004.04.004 pp.71-9
Source: PubMed

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.

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    Article: Progesterone receptors: form and function in brain.
    Roberta Diaz Brinton, Richard F Thompson, Michael R Foy, Michel Baudry, Junming Wang, Caleb E Finch, Todd E Morgan, Christian J Pike, Wendy J Mack, Frank Z Stanczyk, Jon Nilsen
    [show abstract] [hide abstract]
    ABSTRACT: Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRbeta and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and/or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging.
    Frontiers in Neuroendocrinology 06/2008; 29(2):313-39. · 11.43 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

2-month-old Wr mice
 
4-month-old Wr mice
 
age-matched controls
 
four-month-old Wr mice
 
low number
 
motoneuron degeneration
 
NADPHD-active motoneurons
 
nicotinamide adenine dinucleotide phosphate-diaphorase
 
nitric oxide synthesizing enzyme
 
NOS activity
 
PROG neuroprotection
 
reactive species
 
single 20-mg PROG pellet
 
spinal cord
 
stabilization stages
 
steroid neuroprotection
 
symptomatic stage
 
vacuolated degenerating cells
 
vacuolated phenotype
 
Wr mice