title: Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat.
abstract: Diminished glucocorticoid signaling is associated with an age-related decline in hippocampal functioning. In this study we demonstrate the effect of intermittent, every other day (EOD) feeding on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar rats. In aged ad libitum-fed rats, a decrease in the level of total GR and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged rats subjected to EOD feeding, starting from 6 months of age, showed an increase in GR and pGR levels and a higher content of hippocampal corticosterone. Furthermore, prominent nuclear staining of pGR was observed in CA1 pyramidal and DG granule neurons of aged EOD-fed rats. These changes were accompanied by increased Sgk-1 and decreased GFAP transcription, pointing to upregulated transcriptional activity of GR. EOD feeding also induced an increase in the expression of the mineralocorticoid receptor. Our results reveal that intermittent feeding restores impaired GR signaling in the hippocampus of aged animals by inducing rather than by stabilizing GR signaling during aging.
authors.affiliation: Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Tesic
authors.affiliation: Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Milka
authors.initials: M
authors.lastname: Perovic
authors.affiliation: Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Divna
authors.initials: D
authors.lastname: Lazic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Snezana
authors.initials: S
authors.lastname: Kojic
authors.affiliation: Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Kosara
authors.initials: K
authors.lastname: Smiljanic
authors.affiliation: Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Sabera
authors.initials: S
authors.lastname: Ruzdijic
authors.affiliation: Serbian Academy of Sciences and Arts, Belgrade, Serbia.
authors.forename: Ljubisav
authors.initials: L
authors.lastname: Rakic
authors.affiliation: Institute for Biological Research, University of Belgrade, Belgrade, Serbia. Electronic address: selkan@ibiss.bg.ac.rs.
authors.forename: Selma
authors.initials: S
authors.lastname: Kanazir
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000032:analysis / Q000378:metabolism; D000375:Aging; D000818:Animals; D003345:Corticosterone / Q000032:analysis / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics; D008297:Male; D010770:Phosphotransferases / Q000032:analysis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003345:Corticosterone; D018841:HSP90 Heat-Shock Proteins; D017874:Immediate-Early Proteins; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases; C492235:Cdk5r1 protein, rat
keywords: Aging; Corticosterone; Dietary restriction; Glucocorticoid receptor isoforms; Hippocampus; Intermittent feeding