Biblioteca Hospital 12 de Octubre
Martín Hernández, David Bris, Álvaro G. Mac-Dowell, Karina Soledad García Bueno, Borja Madrigal, José LM Leza, Juan Carlos Caso, Javier Rubén

Modulation of the antioxidant nuclear factor (erythroid 2-derived)-like 2 pathway by antidepressants in rats. [artículo] - Neuropharmacology, 2016 - 103:79-91.

Formato Vancouver:
Martín Hernández D, Bris ÁG, MacDowell KS, García Bueno B, Madrigal JL, Leza JC et al. Modulation of the antioxidant nuclear factor (erythroid 2-derived)-like 2 pathway by antidepressants in rats. Neuropharmacology. 2016 Apr;103:79-91.

PMID: 26686388

Contiene 56 referencias

Patients with major depression who are otherwise medically healthy have activated inflammatory pathways in their organism. 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 antioxidant nuclear transcription factor Nrf2. We aim to explore in a depression-like model the Nrf2 pathway in the prefrontal cortex (PFC) and the hippocampus of rats and to analyze whether antidepressants affect the antioxidant activity of the Nrf2 pathway. 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 of upstream and downstream elements of the Nrf2 pathway and the oxidative damage induced by the CMS. After CMS, there is an inhibition of upstream and downstream elements of the Nrf2 pathway in the PFC (e.g. PI3K/Akt, GPx…). Moreover, antidepressant treatments, particularly desipramine and duloxetine, are able to recover some of these elements and to reduce the oxidative damage induced by the CMS. However, in the hippocampus, Nrf2 pathways are not that affected and antidepressants do not have many actions. In conclusion, 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 and antidepressants have a therapeutic action through this pathway. However, it seems that Nrf2 is not involved in the effects caused by CMS in the hippocampus.

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