MOREAU, Maite M.; PIETROPAOLO, Susanna; EZAN, Jerome; ROBERT, Benjamin J. A.; MIRAUX, Sylvain; MAITRE, Marlene; CHO, Yoon; CRUSIO, Wim E.; MONTCOUQUIOL, Mireille; SANS, Nathalie

doi:10.3390/cells11101601

MOREAU, Maite M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

PIETROPAOLO, Susanna

Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]

EZAN, Jerome

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

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Article de revue

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Cells. 2022-05-10, vol. 11, n° 10, p. 1601

Résumé en anglais

Social behavior is a basic domain affected by several neurodevelopmental disorders, including ASD and a heterogeneous set of neuropsychiatric disorders. The SCRIB gene that codes for the polarity protein SCRIBBLE has been identified as a risk gene for spina bifida, the most common type of neural tube defect, found at high frequencies in autistic patients, as well as other congenital anomalies. The deletions and mutations of the 8q24.3 region encompassing SCRIB are also associated with multisyndromic and rare disorders. Nonetheless, the potential link between SCRIB and relevant social phenotypes has not been fully investigated. Hence, we show that Scribcrc/+ mice, carrying a mutated version of Scrib, displayed reduced social motivation behavior and social habituation, while other behavioral domains were unaltered. Social deficits were associated with the upregulation of ERK phosphorylation, together with increased c-Fos activity. Importantly, the social alterations were rescued by both direct and indirect pERK inhibition. These results support a link between polarity genes, social behaviors and hippocampal functionality and suggest a role for SCRIB in the etiopathology of neurodevelopmental disorders. Furthermore, our data demonstrate the crucial role of the MAPK/ERK signaling pathway in underlying social motivation behavior, thus supporting its relevance as a therapeutic target.< Réduire

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Humans

Mots clés en anglais

Animals

Intracellular Signaling Peptides and Proteins

Genetics

MAP Kinase Signaling System

Mice

Motivation

Mutation

Protein Serine-Threonine Kinases

Metabolism

Signal Transduction

Social Behavior

URI

https://oskar-bordeaux.fr/handle/20.500.12278/140342

DOI

http://dx.doi.org/10.3390/cells11101601

Project ANR

Codage de l'information sociale dans l'hippocampe et la synchronie des réseaux neuronaux dans l'autisme
Développment d'une infrastructure française distribuée coordonnée
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043

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Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway

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Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway

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