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Impaired Hippocampal Neuroligin-2 Function by Chronic Stress or Synthetic Peptide Treatment is Linked to Social Deficits and Increased Aggression

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Impaired Hippocampal Neuroligin-2 Function by Chronic Stress or Synthetic Peptide Treatment is Linked to Social Deficits and Increased Aggression

dc.contributor.author	van der Kooij, Michael A	es_ES
dc.contributor.author	Fantin, Martina	es_ES
dc.contributor.author	Kraev, Igor	es_ES
dc.contributor.author	Korshunova, Irina	es_ES
dc.contributor.author	Grosse, Jocelyn	es_ES
dc.contributor.author	Zanoletti, Olivia	es_ES
dc.contributor.author	Guirado Guillén, Ramón	es_ES
dc.contributor.author	Garcia-Mompó, Clara	es_ES
dc.contributor.author	Nácher Roselló, Juan Salvador	es_ES
dc.contributor.author	Stewart, Michael G	es_ES
dc.contributor.author	Berezin, Vladimir	es_ES
dc.contributor.author	Sandi, Carmen	es_ES
dc.date.accessioned	2015-06-10T08:38:56Z
dc.date.available	2015-06-10T08:38:56Z
dc.date.issued	2014	es_ES
dc.identifier.citation	Neuropsychopharmacology Vol. 39 Issue 5: pp. 1148-1158	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44279
dc.description.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.	es_ES
dc.subject	behavioral science	es_ES
dc.subject	mood	es_ES
dc.subject	anxiety	es_ES
dc.subject	stress disorders	es_ES
dc.subject	neuroligin	es_ES
dc.subject	neuropeptides	es_ES
dc.subject	neuropharmacology	es_ES
dc.subject	social behavior	es_ES
dc.subject	stress	es_ES
dc.subject	aggression	es_ES
dc.subject	chronic restraint stress	es_ES
dc.subject	hippocampus	es_ES
dc.subject	neuroligin	es_ES
dc.subject	sociability	es_ES
dc.title	Impaired Hippocampal Neuroligin-2 Function by Chronic Stress or Synthetic Peptide Treatment is Linked to Social Deficits and Increased Aggression	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1038/npp.2013.315	es_ES
dc.identifier.idgrec	099099	es_ES