Cited by 144Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchEstrogen and related hormone effects

Glucocorticoid receptor protein expression in human hippocampus; stability with age

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Wang, Qian, Van Heerikhuize, Joop, Aronica, Eleonora, Kawata, Mitsuhiro, Seress, Laszlo, Joels, Marian, Swaab, Dick F., Lucassen, Paul J.·2013·Neurobiology of Aging

Abstract

The glucocorticoid receptor (GR) exerts numerous functions in the body and brain. In the brain, it has been implicated, amongst others, in feedback regulation of the hypothalamic-pituitary-adrenal axis, with potential deficits during aging and in depression. GRs are abundantly expressed in the hippocampus of rodent, except for the Ammon's horn (CA) 3 subregion. In rhesus monkey however, GR protein was largely absent from all hippocampal subregions, which prompted us to investigate its distribution in human hippocampus. After validation of antibody specificity, we investigated GRα protein distribution in the postmortem hippocampus of 26 human control subjects (1-98 years of age) and quantified changes with age and sex. In contrast to monkey, abundant GR-immunoreactivity was present in nuclei of almost all neurons of the hippocampal CA subfields and dentate gyrus (DG), although neurons of the CA3 subregion displayed lower levels of immunoreactivity. Colocalization with glial fibrillary acidic protein confirmed that GR was additionally expressed in approximately 50% of the astrocytes in the CA regions, with lower levels of colocalization (approximately 20%) in the DG. With increased age, GR expression remained stable in the CA regions in both sexes, whereas a significant negative correlation was found with age only in the DG of females. Thus, in contrast to the very low levels previously reported in monkey, GR protein is prominently expressed in human hippocampus, indicating that this region can form an important target for corticosteroid effects in human.

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Crossref · 10.1016/j.neurobiolaging.2012.11.019

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Authors
Wang, Q., Van Heerikhuize, J., Aronica, E., Kawata, M., Seress, L., Joels, M., Swaab, D. F., & Lucassen, P. J.
Affiliations
  • University of Amsterdam (NL)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Kyoto Prefectural University of Medicine (JP)
  • Netherlands Institute for Neuroscience (NL)
Corresponding author
Lucassen, Paul J.
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2013-06
Volume
34
Issue
6
Pages
1662-1673
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2142684707
Cited by
144
References
109
Citations by year
2026: 8 · 2025: 6 · 2024: 19 · 2023: 13 · 2022: 7 · 2021: 22 · 2020: 8 · 2019: 5 · 2018: 11 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 6 · 2013: 7
FWCI
5.01
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • UvA-DARE (University of Amsterdam) (submittedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion, other-oa)
Funders
  • Royal Dutch Academy of Sciences
  • ISAO
  • Epilepsy Institute in The Netherlands Foundation (SEIN) Heemstede
  • Nederlandse HersenStichting
  • Internationale Stichting Alzheimer Onderzoek (ISAO)
  • Internationale Parkinson Foundation IPF
  • European Union (NEURAD Program)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
glucocorticoid receptor, hippocampus, aging, sex differences, dentate gyrus, astrocytes, glial fibrillary acidic protein, hypothalamic-pituitary-adrenal axis, corticosteroid effects, postmortem brain
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Aging, Animals, Child, Child, Preschool, Female, Gene Expression Regulation, Hippocampus, Humans, Infant, Male, Middle Aged, Receptors, Glucocorticoid, Rats, Sprague-Dawley, Rats, Protein Stability, Young Adult

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