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- Title
Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway.
- Authors
Moreau, Maïté M.; Pietropaolo, Susanna; Ezan, Jérôme; Robert, Benjamin J. A.; Miraux, Sylvain; Maître, Marlène; Cho, Yoon; Crusio, Wim E.; Montcouquiol, Mireille; Sans, Nathalie
- 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 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.
- Subjects
SOCIAL control; NEURAL tube defects; SPINA bifida; MOTIVATION (Psychology); DELETION mutation
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 10, p1601
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11101601