Normal Aging Modulates the Neurotoxicity of Mutant Huntingtin

Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD), a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt), the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or “normal” aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a β-Galactosidase (β-Gal) reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week) and old (15 month) rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts

Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease

The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3′-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patient

Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease

Recent studies have demonstrated that RNAi is a promising approach for treating autosomal dominant disorders. However, discrimination between wild-type and mutant transcripts is essential, to preserve wild-type expression and function. A single nucleotide polymorphism (SNP) is present in more than 70% of patients with Machado-Joseph disease (MJD). We investigated whether this SNP could be used to inactivate mutant ataxin-3 selectively. Lentiviral-mediated silencing of mutant human ataxin-3 was demonstrated in vitro and in a rat model of MJD in vivo. The allele-specific silencing of ataxin-3 significantly decreased the severity of the neuropathological abnormalities associated with MJD. These data demonstrate that RNAi has potential for use in MJD treatment and constitute the first proof-of-principle for allele-specific silencing in the central nervous syste

Do natural antioxidants protect food lipids in gelled emulsions throughout their life cycle?

International audienc

Assessment of biomass-to-energy chains from the forest to the combustion in individual or district heating boilers

International audienc

Évolution du commerce et utilisation de la voiture. Distribution des biens de consommation et usage de la voiture particulière pour motif achats dans les agglomérations françaises. Rapport final.

Tours : Beauvais ConsultantSince the 1960s the big retail stores and their more recent variations (specialised superstores, maxi-discounts) have spread far and wide across French city suburbs. The average size of these stores has grown steadily as has also their power of attraction. In-deed, they tend to be found on the fringes of agglomerations, near bypasses and access to motorways. This article seeks to describe the shopping habits of their customers on the basis of 14 surveys carried out among 5,000 consumers domiciled in three urban areas, and it leads to an assessment of the effects of the location of these stores on road traffic as well as on concomitant gas emissions. The result of this lengthy evaluation may be summarized in one sentence: carbon dioxide emissions are four times stronger when shopping in a suburban hyper-market than when shopping in a local supermarket.Taking into account the very strong impact on CO2 emissions of the hypermarket situated on the outskirts, the question arises as to whether, in the light of sustainable development, this is the right model to export throughout the world.Les résultats de cette recherche sur l'évolution du commerce et l'usage de la voiture peuvent être résumés en trois points : - Quelles sont les évolutions que connaît la distribution des biens de consommation ? - Quels sont les liens entre les différentes formes de distribution et l'usage de la voiture ? - Quels sont les enjeux en termes de parcours en voiture particulière pour motif " achat " ? Les auteurs ont mis en évidence une diminution du nombre de magasins, une augmentation de leur surface moyenne, une concentration géographique de l'appareil commercial au profit des franges d'agglomération, un développement des livraisons aux particuliers. Par ailleurs, une relation a pu être établie d'une part entre la part de la distance parcourue et la taille du magasin, et d'autre part entre la proportion de déplacements effectues en voiture et la localisation du magasin. La part de la circulation en voiture particulière imputable aux achats a pu être estimée a vingt-trois pour cent de la circulation en voiture particulière dans les agglomérations françaises pour l'année 1999. Enfin, deux scenarios ont été construits a l'horizon 2010 : dans l'un, la circulation imputable aux achats est estimée a 40,4 milliards de véhicules-km, et dans l'autre a 27,8 milliards de véhicules-km, soit trente-et-un pour cent de moins

Évolution du commerce et utilisation de la voiture. Distribution des biens de consommation et usage de la voiture particulière pour motif achats dans les agglomérations françaises. Rapport final.

Les résultats de cette recherche sur l'évolution du commerce et l'usage de la voiture peuvent être résumés en trois points : - Quelles sont les évolutions que connaît la distribution des biens de consommation ? - Quels sont les liens entre les différentes formes de distribution et l'usage de la voiture ? - Quels sont les enjeux en termes de parcours en voiture particulière pour motif " achat " ? Les auteurs ont mis en évidence une diminution du nombre de magasins, une augmentation de leur surface moyenne, une concentration géographique de l'appareil commercial au profit des franges d'agglomération, un développement des livraisons aux particuliers. Par ailleurs, une relation a pu être établie d'une part entre la part de la distance parcourue et la taille du magasin, et d'autre part entre la proportion de déplacements effectues en voiture et la localisation du magasin. La part de la circulation en voiture particulière imputable aux achats a pu être estimée a vingt-trois pour cent de la circulation en voiture particulière dans les agglomérations françaises pour l'année 1999. Enfin, deux scenarios ont été construits a l'horizon 2010 : dans l'un, la circulation imputable aux achats est estimée a 40,4 milliards de véhicules-km, et dans l'autre a 27,8 milliards de véhicules-km, soit trente-et-un pour cent de moins.localisation des magasins ; commerce électronique ; livraisons aux particuliers ; usage de la voiture particulière ; distance parcourue par achat

Retinal cell type expression specificity of HIV-1-derived gene transfer vectors upon subretinal injection in the adult rat: influence of pseudotyping and promoter

International audienc

Montmorillonite for clay-polymer nanocomposites: Intercalation of tailored compounds based on succinic anhydride, acid and acid salt derivatives—a review

International audienceTailored compounds, based on alkyl-substituted derivatives of succinic anhydride, acid and dipotassium salt have been used to evaluate their role for intercalation of montmorillonite (MMT) and the formation of nanocomposites based on polyethylene (PE) in the presence of maleic anhydride grafted polyethylene as compatibilizer. The samples have been prepared via a solution dispersion technique. We found that these tailored compounds can be intercalated into the layers of montmorillonite and expansion of the lattice was confirmed by wide angle X-ray diffraction and FTIR spectra. The higher affinity of the succinic groups for the organoclay has been explained as well as the decrease of the polar function influence on the gallery expansion when increasing the hydrophobicity of the organic compounds