Neurotrophic ACTH analogue promotes plasticity of type I corticosteroid receptor in brain of senescent male rats

J M Reul, J A Tonnaer, E R De Kloet

Research output: Contribution to journalArticle (Academic Journal)

84 Citations (Scopus)

Abstract

Age-related changes were studied in the concentration of type-I and type-II corticosteroid receptors in the hippocampus of young adult (3 months) and aged (28.5 to 30.5 months) male rats. Using 3H-labelled ligands, in vitro binding of type-I and type-II corticosteroid receptors in the soluble cell fraction (cytosol) revealed an age-related decrease in concentration of both receptor types of 52% and 28%, respectively. Infusion of young and aged male rats for 2 weeks with the ACTH4-9 [adrenocorticotropin4-9] peptide analogue ORG 2766 (0.5 micrograms/0.5 microliter/hr) resulted in only a minor increase (+8%) in the number of type-I receptors in young rats. In the aged animals, however, the type-I receptor concentration was 68% higher than in the vehicle-treated aged animals. In contrast, no effect of the peptide treatment was noted on the concentration of type-II receptors in either young or aged rats. Furthermore, no effect was found for either age or treatment with peptide on the affinity of type-I and type-II receptors for their respective ligands. Binding of 3H-labelled ligands to brain sections of young and aged rats was performed using in vitro autoradiography. Quantitative image analysis of the film showed that in senescence there is a marked reduction in both type-I (62-75%) and type-II (29-56%) receptor concentrations in the hippocampal subregions (CA1, CA2, CA3 and dentate gyrus) as well as in the lateral septum. Treatment of aged rats with ORG 2766 selectively reversed the age-associated reduction in type-I receptors, while the peptide did not affect the type-II receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)253-60
Number of pages8
JournalNeurobiology of Aging
Volume9
Issue number3
Publication statusPublished - 1 May 1988

Keywords

  • Adrenocorticotropic Hormone
  • Aging
  • Animals
  • Anticonvulsants
  • Autoradiography
  • Brain
  • Hippocampus
  • Male
  • Peptide Fragments
  • Rats
  • Rats, Inbred Strains
  • Receptors, Glucocorticoid

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