Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway
MOREAU, Maite M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
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Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MOREAU, Maite M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
ROBERT, Benjamin J. A.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MAITRE, Marlene
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MONTCOUQUIOL, Mireille
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
SANS, Nathalie
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
< Reduce
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Language
EN
Article de revue
This item was published in
Cells. 2022-05-10, vol. 11, n° 10, p. 1601
English Abstract
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 ...Read more >
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.Read less <
Keywords
Humans
English Keywords
Animals
Intracellular Signaling Peptides and Proteins
Genetics
MAP Kinase Signaling System
Mice
Motivation
Mutation
Protein Serine-Threonine Kinases
Metabolism
Signal Transduction
Social Behavior
ANR Project
Codage de l'information sociale dans l'hippocampe et la synchronie des réseaux neuronaux dans l'autisme - ANR-13-SAMA-0012
Développment d'une infrastructure française distribuée coordonnée - ANR-10-INBS-0004
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043
Développment d'une infrastructure française distribuée coordonnée - ANR-10-INBS-0004
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043