RT Journal Article
SR Electronic
T1 Dynamic behavioral and molecular changes induced by chronic stress exposure in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.07.443011
DO 10.1101/2021.05.07.443011
A1 Thomas D. Prevot
A1 Dipashree Chatterjee
A1 Jaime Knoch
A1 Sierra Codeluppi
A1 Keith A. Misquitta
A1 Corey J.E. Fee
A1 Dwight Newton
A1 Hyunjung Oh
A1 Etienne Sibille
A1 Mounira Banasr
YR 2021
UL http://biorxiv.org/content/early/2021/05/08/2021.05.07.443011.abstract
AB Depression is a leading cause of disabilities around the world, and the underlying mechanisms involved in its pathophysiology are broad and complex. Exposure to chronic stress is a risk factor for developing depressive-symptoms and contributes to cellular and molecular changes precipitating the emergence of symptoms. In the brain, excitatory neurons, inhibitory interneurons and supporting astroglial cells are all sensitive to chronic stress exposure and are known to be impaired in depression.Using an animal model of chronic stress, we assessed the impact of variable durations of chronic stress on the emergence of behavioral deficits and associated molecular changes in the prefrontal cortex (PFC), brain region highly sensitive to stress and impaired in depression. Mice were exposed to up to 35 days of chronic restraint stress and were assessed weekly on behavioral tests measuring anxiety and anhedonia. PFC Protein and RNA levels of specific markers of excitatory, inhibitory synapses and astroglia were quantified using western blot and qPCR, respectively. Correlation and integrative network analyses were used to investigated the impact of chronic stress on the different compartments.Results showed that chronic stress induces anxiety-like behaviors within 7 days, while anhedonia-like behaviors were observed only after 35 days. At the molecular level, alterations of many markers were observed, in particular with longer exposure to chronic stress. Finally, correlation analyses and integrative network analyses revealed that male and female mice react differently to chronic stress exposure and that some markers seem to be more correlated to behaviors deficits in males than in females.Our study demonstrate that chronic induces a dynamic changes that can be observed at the behavioral and molecular levels, and that male and female mice, while exhibiting similar symptoms, have different underlying pathologies.Competing Interest StatementThe authors have declared no competing interest.