A complex relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin

Author:

Mendez‐David Indira123ORCID,David Denis Joseph123ORCID,Deloménie Claudine4ORCID,Tritschler Laurent1ORCID,Beaulieu Jean‐Martin5ORCID,Colle Romain67ORCID,Corruble Emmanuelle67ORCID,Gardier Alain Michel1ORCID,Hen René23ORCID

Affiliation:

1. Université Paris‐Saclay, UVSQ, Centre de recherche en Epidémiologie et Santé des Populations (CESP), UMR 1018, CESP‐Inserm, Team Moods, Faculté de Pharmacie, Bâtiment Henri MOISSAN Orsay France

2. Department of Psychiatry Columbia University New York New York USA

3. Division of Integrative Neuroscience New York State Psychiatric Institute New York New York USA

4. UMS‐IPSIT ACTAGen, Inserm, CNRS, Ingénierie et Plateformes au Service de l'Innovation Thérapeutique Université Paris‐Saclay, Bâtiment Henri MOISSAN Orsay France

5. Department of Pharmacology and Toxicology University of Toronto Toronto Ontario Canada

6. CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris‐Saclay Le Kremlin Bicêtre France

7. Service Hospitalo‐Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris‐Saclay, Assistance Publique‐Hôpitaux de Paris, Hôpital de Bicêtre Le Kremlin Bicêtre France

Abstract

AbstractWe investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule β‐arrestin‐2 (β‐Arr2) is required for the antidepressant‐like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and survival of adult‐born granule cells are absent in the β‐Arr2 knockout (KO) mice. To our surprise, fluoxetine induced a dramatic upregulation of the number of doublecortin (DCX)‐expressing cells in the β‐Arr2 KO mice, indicating that this marker can be increased even though AHN is not. We discovered two other conditions where a complex relationship occurs between the number of DCX‐expressing cells compared to levels of AHN: a chronic antidepressant model where DCX is upregulated and an inflammation model where DCX is downregulated. We concluded that assessing the number of DCX‐expressing cells alone to quantify levels of AHN can be complex and that caution should be applied when label retention techniques are unavailable.

Funder

Fondation Pierre Deniker pour la Recherche et la Prévention en Santé Mentale

National Alliance for Research on Schizophrenia and Depression

Publisher

Wiley

Subject

Cognitive Neuroscience

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