title: Neuroligin-2 Expression in the Prefrontal Cortex is Involved in Attention Deficits Induced by Peripubertal Stress.
abstract: Emerging evidence indicates that attention deficits, which are frequently observed as core symptoms of neuropsychiatric disorders, may be elicited by early life stress. However, the mechanisms mediating these stress effects remain unknown. The prefrontal cortex (PFC) has been implicated in the regulation of attention, including dysfunctions in GABAergic transmission, and it is highly sensitive to stress. Here, we investigated the involvement of neuroligin-2 (NLGN-2), a synaptic cell adhesion molecule involved in the stabilization and maturation of GABAergic synapses, in the PFC in the link between stress and attention deficits. First, we established that exposure of rats to stress during the peripubertal period impairs attention in the five-choice serial reaction time task and results in reductions in the GABA-synthesizing enzyme glutamic acid decarboxylase in different PFC subregions (ie, prelimbic (PL), infralimbic, and medial and ventral orbitofrontal (OFC) cortex) and in NLGN-2 in the PL cortex. In peripubertally stressed animals, NLGN-2 expression in the PL and OFC cortex correlated with attention measurements. Subsequently, we found that adeno-associated virus-induced rescue of NLGN-2 in the PFC reverses the stress-induced attention deficits regarding omitted trials. Therefore, our findings highlight peripuberty as a period that is highly vulnerable to stress, leading to the development of attention deficits and a dysfunction in the PFC GABAergic system and NLGN-2 expression. Furthermore, NLGN-2 is underscored as a promising target to treat stress-induced cognitive alterations, and in particular attentional deficits as manifested by augmented omissions in a continuous performance task.
authors.affiliation: Department of Life Sciences, Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Stamatina
authors.initials: S
authors.lastname: Tzanoulinou
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: García-Mompó
authors.affiliation: Department of Life Sciences, Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Orbicia
authors.initials: O
authors.lastname: Riccio
authors.affiliation: Department of Life Sciences, Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Grosse
authors.affiliation: Department of Life Sciences, Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Zanoletti
authors.affiliation: Department of Informatics, University of Piraeus, Piraeus, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Dedousis
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Valencia, Spain.|CIBERSAM: Spanish National Network for Research in Mental Health, Madrid, Spain.|Fundacion Investigacion Hospital Clinico de Valencia, INCLIVA, Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Nacher
authors.affiliation: Department of Life Sciences, Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
mesh_terms: D000818:Animals; D001288:Attention / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus; D004195:Disease Models, Animal; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000254:growth & development* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C098003:neuroligin 2; D005680:gamma-Aminobutyric Acid