title: Sexually dimorphic long-term effects of an early life experience on AMPA receptor subunit expression in rat brain.
abstract: Neonatal handling, an experimental model of early life experiences, is known to affect hypothalamic-pituitary-adrenal (HPA) axis function, thus increasing adaptability, coping with stress, cognitive abilities and in general brain plasticity-related processes. AMPA receptors (AMPARs) mediate fast synaptic transmission at excitatory glutamatergic synapses in the CNS and are crucial during neuronal development, synaptic plasticity and structural remodeling. AMPARs are composed of four types of subunits, designated as AMPA glutamate receptor subunits (GluA1, GluA2, GluA3 and GluA4), which combine to form tetramers. The present study addressed the question of whether neonatal handling (15min daily maternal separation from postnatal day 1 (PND1) to PND21) might have an effect on GluA1-4 mRNA levels in adult rat male and female brain using in situ hybridization. We have identified selective sexually dimorphic effects of neonatal handling on the mRNA expression levels of AMPAR subunits in adult rat hippocampus and nuclei of the amygdaloid complex. In the dorsal hippocampus GluA1 mRNA levels were increased in handled males, while they were decreased in handled female animals. In the ventral hippocampus and the amygdaloid complex GluA2 mRNA was lower in handled females, while no effect was observed in handled males. Furthermore, we observed that neonatal handling induced in both sexes decreases of GluA2 mRNA in the dorsal hippocampus, as well as in the somatosensory and occipital cortex, of GluA3 mRNA in most hippocampal areas, amygdaloid complex and cortical regions studied, and of GluA4 mRNA in the ventral hippocampus. These results show that glutamatergic transmission is markedly affected by an early experience. The neonatal handling-induced alterations in AMPAR subunit composition are in line with the increased brain plasticity, the more effective HPA axis function, and in general the more adaptive behavioral phenotype known to characterize the handled animals.
authors.affiliation: Laboratory of Physiology, Medical School, University of Patras, 26504 Patras, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Katsouli
authors.affiliation: Laboratory of Biology-Biochemistry, Faculty of Nursing, University of Athens, 11527 Athens, Greece. Electronic address: astam@nurs.uoa.gr.
authors.forename: A
authors.initials: A
authors.lastname: Stamatakis
authors.affiliation: Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, 26504 Patras, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Giompres
authors.affiliation: Laboratory of Physiology, Medical School, University of Patras, 26504 Patras, Greece; Cozzika Foundation, Souidias 69-71, 11521 Athens, Greece.
authors.forename: E D
authors.initials: ED
authors.lastname: Kouvelas
authors.affiliation: Laboratory of Biology-Biochemistry, Faculty of Nursing, University of Athens, 11527 Athens, Greece.
authors.forename: F
authors.initials: F
authors.lastname: Stylianopoulou
authors.affiliation: Laboratory of Physiology, Medical School, University of Patras, 26504 Patras, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Mitsacos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006234:Handling, Psychological; D008297:Male; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012733:Sex Differentiation / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA
keywords: ACTH; AMPA; AMPA glutamate receptor subunits 1–4; AMPA receptors; AMPARs; ANOVA; Ba; CRH; CeA; GluA1–4; HPA axis; IL; LTP; MeA; N-methyl-d-aspartate; NMDA; Occip; PBS; PND; PrL; RT; SEM; Sms In; Sms Out; Str; Striatum; adrenocorticotropin; analysis of variance; basal amygdaloid nucleus; brain plasticity; brief maternal separation; central amygdaloid nucleus; corticotropin-releasing hormone; dCA1; dCA3; dDG; dorsal dentate gyrus; dorsal field 1 of Ammon’s horn; dorsal field 3 of Ammon’s horn; early handling; hypothalamic–pituitary–adrenal axis; in situ hybridization; infralimbic cortex; limbic system; long-term potentiation; medial amygdaloid nucleus; neonatal handling; occipital cortex; phosphate-buffered saline; postnatal day; prelimbic cortex; room temperature; somatosensory inner layers; somatosensory outer layers; standard error of the mean; vCA1; vCA3; vDG; ventral dentate gyrus; ventral field 1 of Ammon’s horn; ventral field 3 of Ammon’s horn; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid