Duloxetine prevents the effects of prenatal stress on depressive‐like and anxiety‐like behavior and hippocampal expression of pro‐inflammatory cytokines in adult male offspring rats

Abstract

Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions.

Musculoskeletal Disorders: Prevalence and Associated Factors among District Hospital Nurses in Haiphong, Vietnam

“…From a psychological perspective, looking after patients with chronic diseases is associated with anxiety [ 45 ]. Biologically, anxiety is associated with inflammation [ 46 , 47 ]. Nevertheless, majority of people suffering from anxiety fail to acknowledge the underlying psychiatric conditions and result in delayed treatment.…”

Adolescent escitalopram prevents the effects of maternal separation on depression‐ and anxiety‐like behaviours and regulates the levels of inflammatory cytokines in adult male mice

“…Cytokines play an important role in mental disorders, and an imbalance between the pro-and anti-inflammatory cytokines may induce inflammatory responses, oxidative and nitrosative stress, as well as affect neurogenesis (Kubera et al, 2011). The HPV and PFC are involved in emotional processing (Cardinal et al, 2002;Fanselow and Dong, 2010;Vertes, 2006), and inflammation of the HPV and PFC may lead to depression and anxiety (Miller et al, 2013;Yang et al, 2013;Zhang et al, 2016), which was our rationale for studying these brain areas. The present study found that MS increased the levels of IL-1β in the HPV, PFC, and serum, and decreased the levels of IL-10 in the HPV in adult offspring.…”

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

“…What is not clear is if this reduction in serum concentrations of pro‐inflammatory cytokines results reduced inflammation within the brain of human subjects. Duloxetine has been shown to suppress pro‐inflammatory cytokines in the hippocampus of adolescent rats (X. Zhang et al, ). Sertraline prevents induction of IL‐β and TNF‐α by seizure activity in the rat hippocampus (Sitges, Gómez, & Aldana, ).…”

“…Duloxetine has been shown to suppress pro-inflammatory cytokines in the hippocampus of adolescent rats (X. Zhang et al, 2016). Sertraline prevents induction of ILβ and TNF-α by seizure activity in the rat hippocampus (Sitges, Gómez, & Aldana, 2014).…”