RT Journal Article
SR Electronic
T1 A non-linear relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.26.115873
DO 10.1101/2020.05.26.115873
A1 Indira Mendez-David
A1 Denis J David
A1 Claudine Deloménie
A1 Jean-Martin Beaulieu
A1 Alain M. Gardier
A1 René Hen
YR 2020
UL http://biorxiv.org/content/early/2020/05/28/2020.05.26.115873.abstract
AB We 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 β2-arrestin is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and on survival of adult-born granule cells are absent in the β2-arrestin knockout (β2-Arr KO) mice. To our surprise fluoxetine induced a dramatic upregulation of doublecortin (DCX) in the β2-Arr KO mice, indicating that DCX expression can be increased even though AHN is not. We discovered two other conditions where DCX expression is regulated non linearly compared to levels of AHN: a chronic stress model where DCX is upregulated and an inflammation model where DCX is down regulated. We conclude that assessing DCX expression alone to quantify levels of AHN can be misleading and that caution should be applied when label retention techniques are not available.HIGHLIGHTSβ2-arrestin (β-Arr2) is required for the antidepressant-like effects of fluoxetine.A dramatic upregulation of doublecortin (DCX) is observed in the β2-Arr KO mice after antidepressant treatment whereas its effects on proliferation of neural progenitors and on survival of adult-born granule cells are absent.DCX is more upregulated than the number of young neurons in a mouse model of depression.DCX is more down regulated than the number of young neurons in a model of inflammation.microRNAs (miRs) may contribute to the regulation of DCX mRNA expression.Competing Interest StatementDJD serves as a consultant for Lundbeck Inc. DJD receives compensation from Lundbeck and Janssen. RH receives compensation as a consultant for Roche, Lundbeck and Servier in relation to the generation of novel antidepressants.