Modulation of the Nuclear Factor (Erythroid 2-Derived)-Like 2 Pathway by Antidepressants In Rats

Abstract

Introduction

Patients with major depression who are otherwise medically healthy have activated inflammatory pathways. It has been described that depression is not only escorted by inflammation but also by induction of multiple oxidative/nitrosative stress pathways. Nevertheless, there are finely regulated mechanisms involved in preserving cells from damage, such as the nuclear factor Nrf2.

Aims

To explore in a depression-like model the Nrf2 pathway in the prefrontal cortex (PFC) and the hippocampus of rats and to analyze which classic antidepressants affect the antioxidant activity of the Nrf2 pathway.

Methods

Male Wistar rats were exposed to chronic mild stress (CMS) and some of them were treated with desipramine, escitalopram or duloxetine. We studied the expression in the PFC and hippocampus of upstream and downstream elements of the Nrf2 pathway and the oxidative damage induced by the CMS.

Results

After exposure to a CMS protocol, in the PFC, there is an inhibition of upstream and downstream elements of the Nrf2 pathway. Moreover, antidepressant treatments, particularly desipramine and duloxetine, are able to recover some of these elements and to reduce the oxidative damage induced by the depression model. In the hippocampus however, Nrf2 pathways are not that affected and antidepressants do not have many actions.

Conclusions

Nrf2 pathway is differentially regulated by antidepressants in the PFC and hippocampus. The Nrf2 pathway is involved in the oxidative/nitrosative damage detected in the PFC after CMS exposure. However, it seems that Nrf2 is not very involved in the effects caused by the CMS in the hippocampus.

Disclosure of interest

The authors have not supplied their declaration of competing interest.