Article

MALDI reveals membrane lipid profile reversion in MDX mice.

Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Av. de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
Neurobiology of Disease (impact factor: 5.4). 08/2009; 36(2):252-8. DOI:10.1016/j.nbd.2009.07.013 pp.252-8
Source: PubMed

ABSTRACT Duchenne muscular dystrophy (DMD), the most common and severe X-linked myopathy, is characterized by the lack of dystrophin, a sub-sarcolemmal protein necessary for normal muscle functions. In a previous study of the lipid content of skeletal muscles of dystrophic (mdx) mice, the animal model for DMD, by in situ Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry (MALDI-MS), an inversion of the phosphatidylcholine PC34:2/PC34:1 ion peaks intensity ratio was observed between destructured (abnormal fiber morphology) and structured (normal fiber morphology). A possible treatment for this dramatic disease is to introduce an exogenous nitric oxide (NO) donor into the organism, leading to an increase of utrophin and a regression of the dystrophic phenotype. In the present work, after confirmation by tandem mass spectrometry of the structure of these two phospholipids, their intensity ratio inversion was used to evidence a restoration of membrane lipid composition very similar to those of wild-type mice after the treatment of mdx mice with molsidomine, a NO donor. This was associated with the observation by immunohistology of an increase of the regeneration process in the mice.

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    Article: Upregulation of brain utrophin does not rescue behavioral alterations in dystrophin-deficient mice.
    Caroline Perronnet, Carine Chagneau, Pascale Le Blanc, Nathalie Samson-Desvignes, Dominique Mornet, Serge Laroche, Sabine De La Porte, Cyrille Vaillend
    [show abstract] [hide abstract]
    ABSTRACT: Dystrophin, the protein responsible for X-linked Duchenne muscular dystrophy (DMD), is normally expressed in both muscle and brain, which explains that its loss also leads to cognitive deficits. The utrophin protein, an autosomal homolog, is a natural candidate for dystrophin replacement in patients. Pharmacological upregulation of endogenous utrophin improves muscle physiology in dystrophin-deficient mdx mice, and represents a potential therapeutic tool that has the advantage of allowing delivery to various organs following peripheral injections. Whether this could alleviate cognitive deficits, however, has not been explored. Here, we first investigated basal expression of all utrophins and dystrophins in the brain of mdx mice and found no evidence for spontaneous compensation by utrophins. Then, we show that systemic chronic, spaced injections of arginine butyrate (AB) alleviate muscle alterations and upregulate utrophin expression in the adult brain of mdx mice. AB selectively upregulated brain utrophin Up395, while reducing expression of Up113 and Up71. This, however, was not associated with a significant improvement of behavioral functions typically affected in mdx mice, which include exploration, emotional reactivity, spatial and fear memories. We suggest that AB did not overcome behavioral and cognitive dysfunctions because the regional and cellular expression of utrophins did not coincide with dystrophin expression in untreated mice, nor did it in AB-treated mice. While treatments based on the modulation of utrophin may alleviate DMD phenotypes in certain organs and tissues that coexpress dystrophins and utrophins in the same cells, improvement of cognitive functions would likely require acting on specific dystrophin-dependent mechanisms.
    Human Molecular Genetics 03/2012; 21(10):2263-76. · 7.64 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

abnormal fiber morphology
 
animal model
 
DMD
 
dramatic disease
 
Duchenne muscular dystrophy
 
dystrophic phenotype
 
dystrophin
 
intensity ratio inversion
 
lipid content
 
mdx
 
mdx mice
 
normal fiber morphology
 
normal muscle functions
 
possible treatment
 
regeneration process
 
severe X-linked myopathy
 
sub-sarcolemmal protein necessary
 
tandem mass spectrometry
 
two phospholipids
 
utrophin
 

Farida Benabdellah