title: Sex-dependent role of vesicular glutamate transporter 3 in stress-regulation and related anxiety phenotype during the early postnatal period.
abstract: Stress and related disorders are in the focus of interest and glutamate is one of the most important neurotransmitters that can affect these processes. Glutamatergic neurons are characterized by vesicular glutamate transporters (VGluT1-3) among which vGluT3 is unique contributing to the non-canonical, neuromodulatory effect of glutamate. We aimed to study the role of vGluT3 in stress axis regulation and related anxiety during the early postnatal period using knockout (KO) mice with special focus on sex differences. Anxiety was explored on postnatal day (PND) 7-8 by maternal separation-induced ultrasonic vocalization (USV). Stress-hormone levels were detected 60 min after intraperitoneal lipopolysaccharide (LPS) injection 7 days later. Both genotypes gained weight, but on PND 14-15 KO mice pups had smaller body weight compared to wild type (WT). vGluT3 KO mice reacted to an immune stressor with enhanced adrenocorticotropin (ACTH) and corticosterone secretion compared to WT. Although there was a tendency for enhanced anxiety measured by more emitted USV, this did not reach the level of significance. The only sex-related effect was the enhanced corticosterone reactivity in male pups. For the HPA axis regulation in neonates vGluT3 expression seems to be dispensable under basal conditions, but is required for optimal response to immune stressors, most probably through an interaction with other neurotransmitters. Disturbance of the fine balance between these systems may result in a borderline enhanced anxiety-like behavior in vGluT3 KO pups.
authors.affiliation: a Hungarian Academy of Sciences, Institute of Experimental Medicine , Budapest , Hungary ;|b János Szentágothai School of Neurosciences, Semmelweis University , Budapest , Hungary ;
authors.forename: Diána
authors.initials: D
authors.lastname: Balázsfi
authors.affiliation: a Hungarian Academy of Sciences, Institute of Experimental Medicine , Budapest , Hungary ;
authors.forename: Lívia
authors.initials: L
authors.lastname: Farkas
authors.affiliation: a Hungarian Academy of Sciences, Institute of Experimental Medicine , Budapest , Hungary ;
authors.forename: Péter
authors.initials: P
authors.lastname: Csikota
authors.affiliation: a Hungarian Academy of Sciences, Institute of Experimental Medicine , Budapest , Hungary ;|b János Szentágothai School of Neurosciences, Semmelweis University , Budapest , Hungary ;
authors.forename: Anna
authors.initials: A
authors.lastname: Fodor
authors.affiliation: c Behaviuor Ecology Research Group, Department of Systematic Zoology and Ecology , Eötvös Loránd University , Budapest , Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Zsebők
authors.affiliation: a Hungarian Academy of Sciences, Institute of Experimental Medicine , Budapest , Hungary ;
authors.forename: József
authors.initials: J
authors.lastname: Haller
authors.affiliation: a Hungarian Academy of Sciences, Institute of Experimental Medicine , Budapest , Hungary ;
authors.forename: Dóra
authors.initials: D
authors.lastname: Zelena
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D014828:Vocalization, Animal
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D003345:Corticosterone; D018698:Glutamic Acid; C504941:Slc17a8 protein, mouse
keywords: Adrenocorticotropin; corticosterone; lipopolysaccharide; pup; ultrasonic vocalization