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Status |
Public on May 11, 2018 |
Title |
Wnt-signaling pathways are dysregulated in female cerebellum following an early methyl donor deficiency in a rat nutritional model |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by array
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Summary |
Early methyl donor –especially B9 and B12 vitamins- deficiency (MDD) is involved in birth defects and brain development retardation. Molecular mechanisms that take place in response to MDD still remain not well understood. In this study we took advantage of a rat nutritional MDD model and performed a microarray analysis on female cerebellum, in order to identify which genes and molecular pathways are disrupted in response to MDD. We found that cerebellum development is altered, with a decrease of the granular cell layer thickness in cerebellum at P21. Furthermore, we investigated the involvement of Wnt-signaling pathway –a major molecular pathway involved in neuronal development but also later in synaptic assembly and neurotransmission. We found that Wnt canonical and Ca2+ pathways are disrupted following early MDD. Notably, we identified GSK3β as a pivotal player affected by MDD, affecting synaptic assembly and signaling. These results could explain the structural brain defects previously observed in response to early MDD and identify new genes and a new molecular pathway that is affected following nutritional methyl donor deprivation.
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Overall design |
One month before pregnancy, female rats were either fed with a standard diet (control - CTRL), or with a diet deficient in folate and vitamin B12 and lowered in choline (methyl donor deficiency - MDD). These diets were maintained until the offspring was weaned at postnatal day 21. Rat pups were euthanized at postnatal day 21, cerebellums were harvested and constituted biological replicates for both CTRL and MDD models.
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Contributor(s) |
Willekens J, Dreumont N, Hergalant S |
Citation(s) |
29804229 |
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Submission date |
Sep 22, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Sebastien Hergalant |
Organization name |
INSERM
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Department |
Bioinformatics
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Lab |
NGERE
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Street address |
Faculté de Médecine. 9 avenue de la forêt de Haye
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City |
Vandoeuvre-lès-Nancy |
ZIP/Postal code |
54505 |
Country |
France |
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Platforms (1) |
GPL14797 |
Agilent-028279 SurePrint G3 Rat GE 8x60K Microarray (Feature Number version) |
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Samples (7)
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GSM2790954 |
control_cerebellum_female_rat_21days_biological_replicate1 |
GSM2790955 |
control_cerebellum_female_rat_21days_biological_replicate2 |
GSM2790956 |
control_cerebellum_female_rat_21days_biological_replicate3 |
GSM2790957 |
control_cerebellum_female_rat_21days_biological_replicate4 |
GSM2790958 |
MDD_cerebellum_female_rat_21days_biological_replicate1 |
GSM2790959 |
MDD_cerebellum_female_rat_21days_biological_replicate2 |
GSM2790960 |
MDD_cerebellum_female_rat_21days_biological_replicate3 |
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Relations |
BioProject |
PRJNA411842 |