Influence of maternal protein malnutrition on oxidative stress and regulators of mitochondrial biogenesis in female rat hearts over succeeding generations.

AIMS: We sought to evaluate the effects of maternal protein restriction (LP) on oxidative balance and transcription factors for mitochondrial biogenesis in the hearts of young female rats of both the first (F1) and second (F2) generation. MAIN METHODS: We evaluated oxidative stress biomarkers (lipid peroxidation and protein oxidation), enzymatic antioxidant defense (activity of superoxide dismutase-SOD, catalase, and glutathione-S-transferase-GST), nonenzymatic antioxidant defense (reduced glutathione-GSH and sulfhydryl groups) and gene expression of AMPK, PGC-1α and TFAM. KEY FINDINGS: Interestingly, lipid peroxidation was decreased (49%, p < 0.001) in the LP-F1 group and 59% (p < 0.001) in LP-F2. In enzymatic defense, we observed increases in SOD activity in the LP-F1 group (79%, p = 0.036) and in CAT activity (approximately 40%, p = 0.041). GSH was increased in F2 in both groups (LP 546%, p < 0.0001 and in NP 491.7%, p < 0.0001). With respect to mitochondrial biogenesis gene transcription, we observed a decrease in AMPK (60%, p < 0. 0001) and an increase in PGC-1α (340%, p < 0.001) in LP compared to NP in the F1 generation. TFAM was decreased in LP-F2L compared to NP-F2L (42%, p = 0.0069) and increased in LP-F2 compared to LP-F1 (160%, p = 0.0037). SIGNIFICANCE: Our study contributes to knowledge of inheritance, showing that despite the potential mitochondrial 'inheritance' of cardiovascular damage caused by maternal malnutrition, that damage is not cross-generational and can be eliminated with proper nutrition in the F1 generation.

Serotonin transporter inhibition during neonatal period induces sex-dependent effects on mitochondrial bioenergetics in the rat brainstem.

The serotonin reuptake is mainly regulated by the serotonin transporters (SERTs), which are abundantly found in the raphe nuclei, located in the brainstem. Previous studies have shown that dysfunction in the SERT has been associated with several disorders, including depression and cardiovascular diseases. In this manuscript, we aimed to investigate how gender and the treatment with a serotonin selective reuptake inhibitor (SSRI) could affect mitochondrial bioenergetics and oxidative stress in the brainstem of male and female rats. Fluoxetine, our chosen SSRI, was used during the neonatal period (i.e., from postnatal Day 1 to postnatal Day 21-PND1 to PND21) in both male and female animals. Thereafter, experiments were conducted in adult rats (60 days old). Our results demonstrate that, during lactation, fluoxetine treatment modulates the mitochondrial bioenergetics in a sex-dependent manner, such as improving male mitochondrial function and female antioxidant capacity.

Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain.

During their reproductive years women produce significant levels of estrogens, predominantly in the form of estradiol, that are thought to play an important role in cardioprotection. Mechanisms underlying this action include both estrogen-mediated changes in gene expression, and post-transcriptional activation of protein signaling cascades in the heart and in neural centers controlling cardiovascular function, in particular, in the brainstem. There, specific neurons, especially those of the bulbar region play an important role in the neuronal control of the cardiovascular system because they control the outflow of sympathetic activity and parasympathetic activity as well as the reception of chemical and mechanical signals. In the present review, we discuss how estrogens exert their cardioprotective effect in part by modulating the actions of internally generated products of cellular oxidation such as reactive oxygen species (ROS) in brain stem neurons. The significance of this review is in integrating the literature of oxidative damage in the brain with the literature of neuroprotection by estrogen in order to better understand both the benefits and limitations of using this hormone to prevent cardiovascular disease.