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Impaired hippocampal Neuroligin-2 Function by chronic stress or synthetic peptide treatment is linked to social deficits and increased aggression

van der Kooij, Michael A.; Fantin, Martina; Kraev, Igor; Korshunova, Irina; Grosse, Jocelyn; Zanoletti, Olivia; Guirado, Ramon; Garcia-Mompó, Clara; Nacher, Juan; Stewart, Michael; Berezin, Vladimir and Sandi, Carmen (2014). Impaired hippocampal Neuroligin-2 Function by chronic stress or synthetic peptide treatment is linked to social deficits and increased aggression. Neuropsychopharmacology, 39(5) pp. 1148–1158.

DOI (Digital Object Identifier) Link: https://doi.org/10.1038/npp.2013.315
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Abstract

Neuroligins (NLGNs) are cell adhesion molecules that are important for proper synaptic formation and functioning, and are critical regulators of the balance between neural excitation/inhibition (E/I). Mutations in NLGNs have been linked to psychiatric disorders in humans involving social dysfunction and are related to similar abnormalities in animal models. Chronic stress increases the likelihood for affective disorders and has been shown to induce changes in neural structure and function in different brain regions, with the hippocampus being highly vulnerable to stress. Previous studies have shown evidence of chronic stress-induced changes in the neural E/I balance in the hippocampus. Therefore, we hypothesized that chronic restraint stress would lead to reduced hippocampal NLGN-2 levels, in association with alterations in social behavior. We found that rats submitted to chronic restraint stress in adulthood display reduced sociability and increased aggression. This occurs along with a reduction of NLGN-2, but not NLGN-1 expression (as shown with western blot, immunohistochemistry, and electron microscopy analyses), throughout the hippocampus and detectable in different layers of the CA1, CA3, and DG subfields. Furthermore, using synthetic peptides that comprise sequences in either NLGN-1 (neurolide-1) or NLGN-2 (neurolide-2) involved in the interaction with their presynaptic partner neurexin (NRXN)-1, intra-hippocampal administration of neurolide-2 led also to reduced sociability and increased aggression. These results highlight hippocampal NLGN-2 as a key molecular substrate regulating social behaviors and underscore NLGNs as promising targets for the development of novel drugs for the treatment of dysfunctional social behaviors.

Item Type: Journal Item
Copyright Holders: 2012 American College of Neuropsychopharmacology
ISSN: 1740-634X
Project Funding Details:
Funded Project NameProject IDFunding Body
MemstickNot SetEUFP7
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Research Group: Centre for Research in Computing (CRC)
Item ID: 39342
Depositing User: Michael Stewart
Date Deposited: 28 Jan 2014 16:44
Last Modified: 21 May 2019 14:50
URI: http://oro.open.ac.uk/id/eprint/39342
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