Neurocentre Magendie

Pauline DELAGE


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4 publication(s) depuis Janvier 2011:

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11/2015 | Hippocampus   IF 4.1
Effects of spaced learning in the water maze on development of dentate granule cells generated in adult mice.
Trinchero MF, Koehl M, Bechakra M, Delage P, Charrier V, Grosjean N, Ladeveze E, Schinder AF, Abrous DN

New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult-born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here, we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP-expressing retrovirus. Animals were exposed to a reference memory protocol for 10-14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype, and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM. (c) 2015 Wiley Periodicals, Inc.

09/2015 | brain behav   IF 2.1
Genetic deletion of the Histone Deacetylase 6 exacerbates selected behavioral deficits in the R6/1 mouse model for Huntington's disease.
Ragot A, Pietropaolo S, Vincent J, Delage P, Zhang H, Allinquant B, Leinekugel X, Fischer A, Cho YH

INTRODUCTION: The inhibition of the Histone Deacetylase 6 (HDAC6) increases tubulin acetylation, thus stimulating intracellular vesicle trafficking and brain-derived neurotrophic factor (BDNF) release, that is, cellular processes markedly reduced in Huntington's disease (HD). METHODS: We therefore tested that reducing HDAC6 levels by genetic manipulation would attenuate early cognitive and behavioral deficits in R6/1 mice, a mouse model which develops progressive HD-related phenotypes. RESULTS: In contrast to our initial hypothesis, the genetic deletion of HDAC6 did not reduce the weight loss or the deficits in cognitive abilities and nest-building behavior shown by R6/1 mice, and even worsened their social impairments, hypolocomotion in the Y-maze, and reduced ultrasonic vocalizations. CONCLUSIONS: These results weaken the validity of HDAC6 reduction as a possible therapeutic strategy for HD. The data are discussed in terms of additional cellular consequences and anatomical specificity of HDAC6 that could explain these unexpected effects.

05/2012 | Neurobiol Aging   IF 5.2
Early development of social deficits in APP and APP-PS1 mice.
Pietropaolo S, Delage P, Lebreton F, Crusio WE, Cho YH

Mimicking relevant behavioral features of the human pathology is one of the most important challenges for animal models of neurological disorders including Alzheimer disease (AD). Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages. It is therefore crucial to identify AD-like behavioral alterations which may reliably reflect the early stages of the pathology, thus permitting tests of more efficient early therapeutic interventions. Here, we demonstrated the very early expression of noncognitive AD-like symptoms, i.e., deficits in social interest, interaction and communication, in APP and APP-PS1 transgenic mice. Conversely, other noncognitive behaviors (sensori-motor gating) as well as cognitive abilities (spontaneous alternation) were unaltered in AD transgenics. Our data suggest that social deficits precede other neuropsychiatric and cognitive AD-like symptoms and can be employed as early markers of AD pathology in genetic mouse models.

2011 | PLoS ONE   IF 3.1
Sex-dependent changes in social behaviors in motor pre-symptomatic R6/1 mice.
Pietropaolo S, Delage P, Cayzac S, Crusio WE, Cho YH

BACKGROUND: The R6/1 mouse line is one of the most widely employed models of Huntington Disease (HD), a complex syndrome characterized by motor and non-motor deficits. Surprisingly, its behavioral phenotype during the early phases of the pathology when the motor impairments are not manifest yet has been poorly investigated. It is also not clear whether the expression of HD-like symptoms at the pre-motor stage in this mouse model differs between the two sexes. METHODS: Male and female 12 weeks-old R6/1 mice and their wild-type littermates were tested on a battery of tests modeling some of the major neuropsychiatric non-motor symptoms of HD: alterations in social interest, social interaction and communication, as well as disturbances in prepulse inhibition of the acoustic startle response (PPI) and circadian patterns of activity. The lack of motor symptoms was confirmed during the entire experimental period by means of the tail test for clasping. RESULTS: R6/1 mice displayed marked alterations in all social behaviors which were mainly observed in males. Male R6/1 animals were also the only ones showing reduced body weight. Both male and female transgenic mice displayed mild alterations in the circadian activity patterns, but no deficits in PPI. CONCLUSIONS: These results demonstrate the validity of the R6/1 mouse in mimicking selected neuropsychiatric symptoms of HD, the social deficits being the clearest markers of the pre-motor phase of the pathology. Furthermore, our data suggest that male R6/1 mice are more suitable for future studies on the early stages of HD.