title: Hippocampus remodeling by chronic stress accompanied by GR, proteasome and caspase-3 overexpression.
abstract: Chronic stress is a threat to homeostasis for many brain regions. While hippocampal formation is one of the most stress-sensitive areas of the cortex, molecular changes occurring as a result of increased glucocorticoid neurotoxicity in hippocampus are largely unknown. The aim of these studies was to investigate mRNA expression of mineralocorticoid and glucocorticoid receptors (MR, GR), proteasome subunits β5 (constitutive subunit) and β1i (inducible immunoproteasome subunit), mTOR (mammalian target of rapamycin), bcl-2; as well as caspase-3 immunoreactivity (confocal microscopy) in adult Wistar rat hippocampus following 10-day restraint stress (plastic restrainers, 6h daily). Chronic restraint led to a significant reduction in number of neuronal and astroglial cells in hippocampal regions CA1-3. This reaction was combined with substantial increase in GR and decrease in MR mRNA levels with the greatest response - 1.5-fold amplitude increase - observed in dentate gyrus and CA3 correspondingly. Stress did not change the expression of constitutive β5 subunit but dramatically enhanced expression of inducible β1i subunit and increased mTOR, and bcl-2 mRNA expression. Multiple scattered cells demonstrating caspase-3(+) profile were found in hippocampus of stressed animals. The study demonstrates that hippocampal remodeling induced by chronic restraint stress is associated with GR, immunoproteasome, mTOR, caspase-3 and bcl-2 overexpression in hippocampus.
authors.affiliation: State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev 01024,Ukraine. Electronic address: dr.orlovsky@gmail.com.
authors.forename: M A
authors.initials: MA
authors.lastname: Orlovsky
authors.affiliation: State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev 01024,Ukraine.
authors.forename: V E
authors.initials: VE
authors.lastname: Dosenko
authors.affiliation: Laboratories for Integrative Neuroscience and Endocrinology, Bristol University, Bristol, Great Britain.
authors.forename: F
authors.initials: F
authors.lastname: Spiga
authors.affiliation: State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev 01024,Ukraine.
authors.forename: G G
authors.initials: GG
authors.lastname: Skibo
authors.affiliation: Laboratories for Integrative Neuroscience and Endocrinology, Bristol University, Bristol, Great Britain.
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism*; D002908:Chronic Disease; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000473:pathology / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; C071313:LMP-2 protein; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C478803:Psmb5 protein, rat
keywords: Chronic stress; Glucocorticoid receptors; Hippocampus; Mineralocorticoid receptors; Restraint stress