Abstract
INTRODUCTION: Studies have demonstrated that insults during development increase the risk for developing diseases later in life, including hypertension, ischemic heart disease, stroke, respiratory disease, diabetes, cancer, as well as psychiatric disorders. Hence, as mitochondrial dysfunction-induced oxidative stress has been proposed to be a central molecular hub linking metabolic and oxidative stress pathways, the serotonin modulation-related mitochondrial boost might mitigate such impairments. Thus, the present study investigates the effects of serotonina modulation by uoxetine on oxidative stress and mitochondrial biogenesis biomarkers in the brainstem and heart of male rats that were overfed during lactation period. METHODS: Normo and overfed animals received uoxetine (FX, SSRI) or saline from postnatal day 39 to postnatal day 59, wherein tissues were collected 24 hours later. RESULTS AND DISCUSSION: Overfeeding increased body weight and induced lipid peroxidation and protein oxidation in both tissues, while genes related to mitochondrial dynamics (PGC1a and TFAM) were speci cally modulated, suggesting a targeted effect of uoxetine on mitochondrial biogenesis pathways by overfeeding across the tissues. Together, our results suggest that early life overfeeding deregulates oxidative balance and mitochondrial biogenesis, wherein FX administration acts toward molecular normalization both in heart and brainstem of male offspring. These ndings shed light on the potential of serotonin modulation to mitigate the effects of overnutrition during developmental periods.