Intrauterine and lactation exposure to fluoxetine blunted in the offspring the aortic adaptive response induced by acute restraint stress

Marques, Bruno V D; Higashi, Carolina Matias; Novi, Daniella R.B. da S.; Zanluqui, Nágela Ghabdan; Gregório, Thais F.; Pinge‐Filho, Phileno; Gerardin, Daniela Cristina Ceccatto; Pelosi, Gislaine Garcia; Moreira, Estefânia Gastaldello; Ceravolo, Graziela Scalianti

doi:10.1016/j.ejphar.2017.08.018

“…Mental stress can induce NOX activation in the endothelium of thoracic aorta [ 63 ] and increase the expression of NOX-4 in carotid [ 64 , 65 ]. This study shows the NOX activation in the brain vessels and the expression of NOX subunits in mRNA and protein levels upon mental stress.…”

Section: Discussionmentioning

confidence: 99%

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

Zhu

¹

,

Haddad

²

,

Yun

³

et al. 2023

Mediators of Inflammation

2

1

0

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Background. Cerebrovascular disease (CVD) is recognized as the leading cause of permanent disability worldwide. Depressive disorders are associated with increased incidence of CVD. The goal of this study was to establish a chronic restraint stress (CRS) model for mice and examine the effect of stress on cerebrovascular inflammation and oxidative stress responses. Methods. A total of forty 6-week-old male C57BL/6J mice were randomly divided into the CRS and control groups. In the CRS group ( n = 20 ), mice were placed in a well-ventilated Plexiglas tube for 6 hours per day for 28 consecutive days. On day 29, open field tests (OFT) and sucrose preference tests (SPT) were performed to assess depressive-like behaviors for the two groups ( n = 10 /group). Macrophage infiltration into the brain tissue upon stress was analyzed by measuring expression of macrophage marker (CD68) with immunofluorescence in both the CRS and control groups ( n = 10 /group). Cerebral microvasculature was isolated from the CRS and controls ( n = 10 /group). mRNA and protein expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and macrophage chemoattractant protein-1 (MCP-1) in the brain vessels were measured by real-time PCR and Western blot ( n = 10 /group). Reactive oxygen species (ROS), hydrogen peroxide (H2O2), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activities were quantified by ELISA to study the oxidative profile of the brain vessels ( n = 10 /group). Additionally, mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in the cerebrovascular endothelium were analyzed by real-time PCR and Western blot ( n = 10 /group). Results. CRS decreased the total distances ( p < 0.05 ) and the time spent in the center zone in OFT ( p < 0.001 ) and sucrose preference test ratio in SPT ( p < 0.01 ). Positive ratio of CD68+ was increased with CRS in the entire region of the brain ( p < 0.001 ), reflecting increased macrophage infiltration. CRS increased the expression of inflammatory factors and oxidative stress in the cerebral microvasculature, including TNF-α ( p < 0.001 ), IL-1β ( p < 0.05 ), IL-6 ( p < 0.05 ), VCAM-1 ( p < 0.01 ), MCP-1 ( p < 0.01 ), ROS ( p < 0.001 ), and H2O2 ( p < 0.001 ). NADPH oxidase (NOX) was activated by CRS ( p < 0.01 ), and mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in brain microvasculature were found to be increased. Conclusions. To our knowledge, this is the first study to demonstrate that CRS induces depressive stress and causes inflammatory and oxidative stress responses in the brain microvasculature.

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“…The recurrent evidence found that maternal exposure to antidepressants brought side effects in aorta reactivity and nitric oxide metabolites. Marques et al (2017 ) confirmed that prenatal fluoxetine exposure blunted the aortic adaptive response in the offspring, indicating a reduction in aortic contraction in the aorta. Previous research has drawn a close relationship between maternal depression and offspring’s high risk of cardiovascular diseases.…”

Section: Association Between Prenatal Drug Exposure and Programmed Ca...mentioning

confidence: 64%

The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease

Wu

¹

,

Zhou

²

,

Hua

³

et al. 2023

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The “developmental origins of health and disease” (DOHaD) hypothesis posits that early-life environmental exposures have a lasting impact on individual’s health and permanently shape growth, structure, and metabolism. This reprogramming, which results from fetal stress, is believed to contribute to the development of adulthood cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and increased susceptibility to ischemic injuries. Recent studies have shown that prenatal exposure to drugs, such as glucocorticoids, antibiotics, antidepressants, antiepileptics, and other toxins, increases the risk of adult-onset cardiovascular diseases. In addition, observational and animal experimental studies have demonstrated the association between prenatal drug exposure and the programming of cardiovascular disease in the offspring. The molecular mechanisms underlying these effects are still being explored but are thought to involve metabolism dysregulation. This review summarizes the current evidence on the relationship between prenatal drug exposure and the risk of adult cardiovascular disorders. Additionally, we present the latest insights into the molecular mechanisms that lead to programmed cardiovascular phenotypes after prenatal drug exposure.

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“…These results suggest that, although fluoxetine may improve endothelial function, other endothelial-independent mechanisms such as nNOS or vasoconstrictor agents may oppose these beneficial effects. To that end, intrauterine exposure of Wistar rats to fluoxetine suppressed the ex vivo aortic hypo-contraction response to stress in offspring [ 35 ]. However, as the authors acknowledged, it is unlikely that the observed reduction in vascular relaxation by fluoxetine was due to endothelial dysfunction because the aortic responses to acetylcholine and phenylephrine were preserved when compared with that in the controls.…”

Section: The Effect Of Antidepressant Treatment On Arteriosclerotic Processes: Experimental Datamentioning

confidence: 99%

Off-Target Effects of Antidepressants on Vascular Function and Structure

Dimoula

¹

,

Fotellis

²

,

Aivalioti

³

et al. 2021

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Depression emerges as a risk factor for cardiovascular disease, and it is thought that successful antidepressant treatment may reduce such a risk. Therefore, antidepressant treatment embodies a potential preventive measure to reduce cardiovascular events in patients with depression. Accumulating evidence indicates that antidepressants have off-target effects on vascular dysfunction and in the early stages of atherosclerosis, which form the basis for cardiovascular disease (CVD) pathogenesis. In this context, we performed a thorough review of the evidence pertaining to the effects of different classes of antidepressant medications on hemodynamic and early atherosclerosis markers. The preclinical and clinical evidence reviewed revealed a preponderance of studies assessing selective serotonin reuptake inhibitors (SSRI), whereas other classes of antidepressants are less well-studied. Sufficient evidence supports a beneficial effect of SSRIs on vascular inflammation, endothelial function, arterial stiffening, and possibly delaying carotid atherosclerosis. In clinical studies, dissecting the hypothesized direct beneficial antidepressant effect of SSRIs on endothelial health from the global improvement upon remission of depression has proven to be difficult. However, preclinical studies armed with appropriate control groups provide evidence of molecular mechanisms linked to endothelial function that are indeed modulated by antidepressants. This suggests at least a partial direct action on vascular integrity. Further research on endothelial markers should focus on the effect of antidepressants on treatment responders versus non-responders in order to better ascertain the possible beneficial vascular effects of antidepressants, irrespective of the underlying course of depression.

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Intrauterine and lactation exposure to fluoxetine blunted in the offspring the aortic adaptive response induced by acute restraint stress

Cited by 4 publications

References 29 publications

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease

Off-Target Effects of Antidepressants on Vascular Function and Structure

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