Neonatal SSRI exposure improves mitochondrial function and antioxidant defense in rat heart

Abstract

Protein restriction during prenatal, postnatal, or in both periods has a close relationship with subsequent development of cardiovascular disease in adulthood. Elevated brain levels of serotonin and its metabolites have been found in malnourished states. The aim in the present study was to investigate whether treatment with fluoxetine (Fx), a selective serotonin reuptake inhibitor, mimics the detrimental effect of low-protein diet during the perinatal period on the male rat heart. Our hypothesis is that increased circulating serotonin as a result of pharmacologic treatment with Fx leads to cardiac dysfunction similar to that observed in protein-restricted rats. Male Wistar rat pups received daily subcutaneous injection of Fx or vehicle from postnatal day 1 to postnatal day 21. Male rats were euthanized at 60 days of age and the following parameters were evaluated in the cardiac tissue: mitochondrial respiratory capacity, respiratory control ratio, reactive oxygen species (ROS) production, mitochondrial membrane potential, and biomarkers of oxidative stress and antioxidant defense. We found that Fx treatment increased mitochondrial respiratory capacity (123%) and membrane potential (212%) and decreased ROS production (55%). In addition we observed an increase in the antioxidant capacity (elevation in catalase activity (5-fold) and glutathione peroxidase (4.6-fold)). Taken together, our results suggest that Fx treatment in the developmental period positively affects the mitochondrial bioenergetics and antioxidant defense in the cardiac tissue.

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

“…306–307 Treating rat pups with 53 improves mitochondrial membrane potential, respiratory capacity, and antioxidant defense in the heart, implicating 48 in mitochondrial health during development. 308 …”

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

“…Body weights were measured at 7th, 14th and 21st day of life, as well as immediately before euthanasia at 60 days of age. Body weights were recorded using an analytical scale (S‐400 with a capacity of 400 g and a readability of 0.01 g; Braz, Freitas, et al., ; Braz, Pedroza, et al., ; Pinheiro et al., ; da Silva et al., ; da Silva, Braz, Silva‐Filho, et al., ; da Silva, Braz, Pedroza, et al., ).…”

“…The pink pigment yielded was measured spectrophotometrically at 535 nm at room temperature ( n = 4–6). The results were expressed as μmol of MDA/mg protein (Braz, Freitas, et al., ; Ferreira et al., ).…”

“…Then, the enzymatic kinetics were analysed during a 2 min period at 480 nm (Misra & Fridovich, ). The results were expressed as U/mg protein (Braz, Freitas, et al., ; Ferreira et al., ).…”

“…Recent research has indicated that neonatal exposure to fluoxetine, another SSRI, increases SERT gene expression and protein content in the hypothalamus of animals at 21 and 40 days of life (Pinheiro et al., ). Studies from our laboratory have highlighted that fluoxetine treatment during critical development period improves mitochondrial function and reduces oxidative stress in several tissues (Braz, Freitas, et al., ; Braz, Pedroza, et al., ; Simoes‐Alves et al., ).…”