Rapid effects of S-ketamine on the morphology of hippocampal astrocytes and BDNF serum levels in a sex-dependent manner.


Journal

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
ISSN: 1873-7862
Titre abrégé: Eur Neuropsychopharmacol
Pays: Netherlands
ID NLM: 9111390

Informations de publication

Date de publication:
03 2020
Historique:
received: 10 06 2019
revised: 13 12 2019
accepted: 02 01 2020
pubmed: 25 1 2020
medline: 11 8 2021
entrez: 25 1 2020
Statut: ppublish

Résumé

The prevalence of major depressive disorder (MDD) is higher in women than men. Importantly, a differential behavioral response by sex to the antidepressant response to ketamine in rodents has been reported. Mechanistically, male depressed-like animals showed an increased spine density after ketamine treatment via restoration of synaptic protein levels while those proteins were not altered in female rats. In addition, preclinical studies indicate that the impairment of astrocytic plasticity is one of the contributing mechanisms in the pathophysiology of MDD. Accordingly, in this study, we determined the effect of sex on the rapid morphological alteration of hippocampal astrocytes and the serum level of BDNF one hour after S-ketamine injection. A single intraperitoneal dose of S-ketamine (15 mg/kg) or saline was injected to the male and female Flinders Sensitive Line (FSL) rats, a genetic animal model of depression and their brains were perfused one hour after treatment. The size of the GFAP positive astrocytes in the hippocampal subregions was measured. The volume of different hippocampal subregions was assessed using the Cavalieri estimator. Moreover, serum levels of BDNF were measured with enzyme-linked immunosorbent assay (ELISA) kits. The volume of hippocampal subregions significantly increased one hour after S-ketamine in both male and female FSL animals. However, a substantial alteration in the morphology of the hippocampal astrocytes was observed only in the female rats. Additionally, significantly increased serum BDNF levels in the female depressed rats were observed one hour after S-ketamine treatment. Our results indicate that the rapid effects of S-ketamine on the morphology of the hippocampal astrocytes and the serum level of BDNF are sex-dependent.

Identifiants

pubmed: 31973999
pii: S0924-977X(20)30003-1
doi: 10.1016/j.euroneuro.2020.01.001
pmc: PMC7281850
mid: NIHMS1595010
pii:
doi:

Substances chimiques

Bdnf protein, rat 0
Biomarkers 0
Brain-Derived Neurotrophic Factor 0
Esketamine 50LFG02TXD
Ketamine 690G0D6V8H

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

94-103

Subventions

Organisme : Intramural NIH HHS
ID : ZIA MH002857
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier B.V. and ECNP. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest All authors declare that they have no conflicts of interest.

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Auteurs

Maryam Ardalan (M)

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark. Electronic address: maryam.ardalan@clin.au.dk.

Betina Elfving (B)

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Ali H Rafati (AH)

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Monireh Mansouri (M)

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran.

Carlos A Zarate (CA)

Experimental Therapeutics and Pathophysiology Branch, National, Institute of Mental Health, National Institutes of Health, Bethesda, USA.

Aleksander A Mathe (AA)

Department of Clinical Neuroscience, Karolinska Institutet, Stockohlm, Sweden.

Gregers Wegener (G)

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa; AUGUST Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

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Classifications MeSH