Neurocentre Magendie

Team publications







IF du Neurocentre
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112 publications

* equal contribution
The indicated IF have been collected by the Web of Sciences in July 2017



18/04/2018 | cell stem cell
Human Adult Neurogenesis: Evidence and Remaining Questions.
Kempermann G, Gage FH, Aigner L, Song H, Curtis MA, Thuret S, Kuhn HG, Jessberger S, Frankland PW, Cameron HA, Gould E, Hen R, Abrous DN, Toni N, Schinder AF, Zhao X, Lucassen PJ, Frisen J

Abstract:
Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.





13/03/2018 | Brain Behav Immun   IF 6
mTORC1 pathway disruption abrogates the effects of the ciliary neurotrophic factor on energy balance and hypothalamic neuroinflammation.
Andre C, Catania C, Remus-Borel J, Ladeveze E, Leste-Lasserre T, Mazier W, Binder E, Gonzales D, Clark S, Guzman-Quevedo O, Abrous DN, Laye S, Cota D

Abstract:
Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammatory responses in the ARC and whether these effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates both energy metabolism and inflammation. To this purpose, chow- and high fat diet (HFD)- fed mice lacking the S6 kinase 1 (S6K1(-/-)), a downstream target of mTORC1, and their wild-type (WT) littermates received 12 days continuous intracerebroventricular (icv) infusion of the CNTF analogue axokine (CNTFAx15). Behavioral, metabolic and molecular effects were evaluated. Central chronic administration of CNTFAx15 decreased body weight and feed efficiency in WT mice only, when fed HFD, but not chow. These metabolic effects correlated with increased number of iba-1 positive microglia specifically in the ARC and were accompanied by significant increases of IL-1beta and TNF-alpha mRNA expression in the hypothalamus. Hypothalamic iNOS and SOCS3 mRNA, molecular markers of pro-inflammatory response, were also increased by CNTFAx15. All these changes were absent in S6K1(-/-) mice. This study reveals that CNTFAx15 requires a functional S6K1 to modulate energy balance and hypothalamic inflammation in a diet-dependent fashion. Further investigations should determine whether S6K1 is a suitable target for the treatment of pathologies characterized by a high neuroinflammatory state.





06/03/2018 | Cell Rep   IF 8.3
Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period.
Donega V, Marcy G, Lo Giudice Q, Zweifel S, Angonin D, Fiorelli R, Abrous DN, Rival-Gervier S, Koehl M, Jabaudon D, Raineteau O

Abstract:
Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal radial glial cells that persist after birth in the dorsal subventricular zone and continue to give rise to cortical neurons, although with low efficiency. Single-cell RNA sequencing reveals a dysregulation of transcriptional programs, which parallels changes in m(6)A methylation and correlates with the gradual decline in cortical neurogenesis observed in vivo. Rescuing experiments show that postnatal progenitors are partially permissive to genetic and pharmacological manipulations. Our study provides an in-depth characterization of postnatal Glu progenitors and identifies potential therapeutic targets for promoting brain repair.





05/03/2018 | Mol Psychiatry   IF 13.2
Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior.
Deroche-Gamonet V, Revest JM, Fiancette JF, Balado E, Koehl M, Grosjean N, Abrous DN, Piazza PV

Abstract:
The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evidence of the causal role of DG neurogenesis in drug-seeking behaviors has not been established. Here we assessed the role of new DG neurons in cocaine self-administration using an inducible transgenic approach that selectively depletes adult DG neurogenesis. Our results show that transgenic mice with decreased adult DG neurogenesis exhibit increased motivation to self-administer cocaine and a higher seeking response to cocaine-related cues. These results identify adult hippocampal neurogenesis as a key factor in vulnerability to cocaine addiction.





09/05/2017 | Mol Psychiatry   IF 13.2
Inducing a long-term potentiation in the dentate gyrus is sufficient to produce rapid antidepressant-like effects.
Kanzari A, Bourcier-Lucas C, Freyssin A, Abrous DN, Haddjeri N, Lucas G

Abstract:
Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects. Thus, Sprague-Dawley rats having undergone a successful LTP displayed a significant reduction of immobility when passed acutely 3 days thereafter in the forced swimming test (FST). Further, in a longitudinal paradigm using the pseudo-depressed Wistar-Kyoto rat strain, LTP elicited a decrease of FST immobility after only 2 days, whereas the AD desipramine was not effective before 16 days. In both models, the influence of LTP was transient, as it was no more observed after 8-9 days. No effects were observed on the locomotor activity or on anxiety-related behavior. Theta-burst stimulation of a brain region anatomically adjacent to the PP remained ineffective in the FST. Immunoreactivity of DG cells for phosphorylated histone H3 and doublecortin were not modified three days after LTP, indicating a lack of effect on both cell proliferation and neurogenesis. Finally, depleting brain serotonin contents reduced the success rate of LTP but did not affect its subsequent AD-like effects. These results confirm the 'plastic DG' theory of rapid AD efficacy. Beyond, they point out stimulations of the entorhinal cortex, from which the PP originates, as putative new approaches in AD research.Molecular Psychiatry advance online publication, 9 May 2017; doi:10.1038/mp.2017.94.





30/11/2016 | Diabetes   IF 8.7
Inhibiting Microglia Expansion Prevents Diet-induced Hypothalamic and Peripheral Inflammation.
Andre C, Guzman-Quevedo O, Rey C, Remus-Borel J, Clark S, Castellanos-Jankiewicz A, Ladeveze E, Leste-Lasserre T, Nadjar A, Abrous DN, Laye S, Cota D

Abstract:
Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. Here we tested whether the intertwining of these two processes has a role in the metabolic changes caused by three weeks of saturated high-fat diet (HFD) consumption.As compared to chow, HFD-fed mice rapidly increased body weight and fat mass, and specifically showed increased microglia number in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet, since feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation. Blocking HFD-induced cell proliferation by central delivery of the antimitotic drug arabinofuranosyl cytidine (AraC) blunted food intake, body weight gain and adiposity. AraC treatment completely prevented the increase in the number of activated microglia in the ARC, the expression of the pro-inflammatory cytokine TNFalpha in microglia and the recruitment of the NF-kappaB pathway, while restoring hypothalamic leptin sensitivity. Central blockade of cell proliferation also normalized circulating levels of the cytokines leptin and IL-1beta and decreased peritoneal pro-inflammatory CD86-IR macrophages number.These findings suggest that inhibition of diet-dependent microglia expansion hinders body weight gain while preventing central and peripheral inflammatory responses due to caloric overload.





25/11/2016 | Sci Rep   IF 4.3
Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress.
Belnoue L, Malvaut S, Ladeveze E, Abrous DN, Koehl M

Abstract:
Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role in the coordination of mother-infant interactions, suggesting that motherhood may be associated to enhanced olfactory performances, and that this effect may be abolished by maternal stress. To test this hypothesis, we analyzed the impact of motherhood under normal conditions or after gestational stress on olfactory functions in C57BL/6 J mice. We report that gestational stress alters maternal behavior and prevents both mothers' ability to discriminate pup odors and motherhood-induced enhancement in odor memory. We investigated adult bulbar neurogenesis as a potential mechanism of the enhanced olfactory function in mothers and found that motherhood was associated with an increased complexity of the dendritic tree of newborn neurons. This motherhood-evoked remodeling was totally prevented by gestational stress. Altogether, our results may thus provide insight into the neural changes that could contribute to altered maternal behavior in stressed mothers.





2016 | PLoS ONE   IF 2.8
LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain.
Tiveron MC, Beurrier C, Ceni C, Andriambao N, Combes A, Koehl M, Maurice N, Gatti E, Abrous DN, Kerkerian-Le Goff L, Pierre P, Cremer H

Abstract:
LAMP5 is member of the LAMP family of membrane proteins. In contrast to the canonical members of this protein family, LAMP1 and LAMP2, which show widespread expression in many tissues, LAMP 5 is brain specific in mice. In C. elegans, the LAMP5 ortholog UNC-46 has been suggested to act a trafficking chaperone, essential for the correct targeting of the nematode vesicular GABA-transporter UNC-47. We show here that in the mouse brain LAMP5 is expressed in subpopulations of GABAergic forebrain neurons in the striato-nigral system and the olfactory bulb. The protein was present at synaptic terminals, overlapping with the mammalian vesicular GABA-transporter VGAT. In LAMP5-deficient mice localization of the transporter was unaffected arguing against a conserved role in VGAT trafficking. Electrophysiological analyses in mutants showed alterations in short term synaptic plasticity suggesting that LAMP5 is involved in controlling the dynamics of evoked GABAergic transmission. At the behavioral level, LAMP5 mutant mice showed decreased anxiety and deficits in olfactory discrimination. Altogether, this work implicates LAMP5 function in GABAergic neurotransmission in defined neuronal subpopulations.





25/11/2015 | Hippocampus   IF 3.9
Running per se stimulates the dendritic arbor of newborn dentate granule cells in mouse hippocampus in a duration-dependent manner.
Dostes S, Dubreucq S, Ladeveze E, Marsicano G, Abrous DN, Chaouloff F, Koehl M

Abstract:
Laboratory rodents provided chronic unlimited access to running wheels display increased neurogenesis in the hippocampal dentate gyrus. In addition, recent studies indicate that such an access to wheels stimulates dendritic arborization in newly formed neurons. However, (i) the presence of the running wheel in the housing environment might also bear intrinsic influences on the number and shape of new neurons and (ii) the dendritic arborization of new neurons might be insensitive to moderate daily running activity (i.e. several hours). In keeping with these uncertainties, we have examined neurogenesis and dendritic arborization in newly formed granular cells in adult C57Bl/6N male mice housed for 3 weeks under standard conditions, with a locked wheel, with a running wheel set free 3 h/day, or with a running wheel set permanently free. The results indicate that the presence of a blocked wheel in the home cage increased cell proliferation, but not the number of new neurons while running increased in a duration-dependent manner the number of newborn neurons, as assessed by DCX labeling. Morphological analyses of the dendritic tree of newborn neurons, as identified by BrdU-DCX co-staining, revealed that although the presence of the wheel stimulated their dendritic architecture, the amplitude of this effect was lower than that elicited by running activity, and was found to be running duration-dependent. This article is protected by copyright. All rights reserved.





11/2015 | Hippocampus   IF 3.9
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

Abstract:
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.