Effects of fluoxetine withdrawal in the brainstem and hypothalamus of overnourished rats: Chronic modulation on oxidative stress levels.

Poor nutritional quality in the early stages of development is associated with neurological diseases in adulthood. Studies showed that obesity-induced oxidative stress contributes to the genesis of neurological diseases through dysregulation of the brainstem and hypothalamus. Fluoxetine (Fx) is an antidepressant member in the family of selective serotonin reuptake inhibitors (SSRI) that can induce positive effects by reducing oxidative damage in brain tissues. We aimed to evaluate the late effect of Fx in the brainstem and hypothalamus of overnourished rats during development. Male Wistar rats, after birth, were randomly divided into the normal-nourished group (N, n = 9) and the overnourished group (O, n = 3). On the 39th day of life, the groups were subdivided into normofed, and the overnourished group treated or not with fluoxetine (10 mg/kg daily) (NF, NV, OF, and OV). All groups were treated from the 39th to the 59th day of life, and within 90 days, the tissues were collected for oxidative stress analysis. Briefly, our results showed that Fx treatment induced a tissue-dependent long-lasting effect in overfed animals, increasing the enzymatic defense (i.e., CAT and GST activity) in the hypothalamus, but more intensive, increasing the non-enzymatic defense (i.e., Total Thiols and GSH levels) in the brainstem. Overall, our study suggests that serotonin modulation at the final stage of brain development causes a long-lasting impact on brain structures in overfed rats at a different mode.

The immediate effect of overnutrition and fluoxetine treatment during the critical period of development on the hippocampus.

It is well known that overnutrition, overweight, and obesity in children can modulate brain mechanisms of plasticity, monoaminergic systems, and mitochondrial function. The immediate effect of overnutrition during the developmental period has not been thoroughly examined in rats until the present. This study sought to evaluate the impact on adult rats of early life overfeeding and fluoxetine treatment from post-natal day 1 (PND1) to post-natal day 21 (PND21) relative to mitochondrial function, oxidative balance, and expression of specific monoaminergic genes in the hippocampus. The following were evaluated: mitochondrial function markers, oxidative stress biomarkers, dopamine-and serotonin-related genes, and BDNF mRNA levels. Overfeeding during the lactation period deregulates cellular metabolism and the monoaminergic systems in the hippocampus. Strikingly, serotonin modulation by fluoxetine treatment protected against some of the effects of early overnutrition. We conclude that overfeeding during brain development induce detrimental effects in mitochondria and in the genes that regulate homeostatic status that can be the molecular mechanisms related to neurological diseases.

Effects of perinatal protein restriction on the oxidative balance in the hypothalamus of 60-day-old rats / Efeitos da restrição proteica perinatal sobre o balanço oxidativo no hipotálamo de ratos de 60 dias de idade

ABSTRACT Objective Evaluate the effects of maternal low-protein diet on the oxidative stress in the hypothalamus of 60-day-old rats. Methods Male Wistar rats were divided into two experimental groups according to the mother's diet during pregnancy and lactation; control group (NP:17% casein n=6) and a malnourished group (LP:8% casein n=6). At 60 days of life, the rats were sacrificed for the collection of the hypothalamus for further biochemical analysis. Results Our results showed an increase in oxidative stress in malnourished group, observed through an increase in carbonyl content (p=0.0357), a reduction in the activity of the glutathione-S-transferase enzyme (p=0.0257), and a reduction in the non-enzymatic antioxidant capacity evidenced by the decrease in the ratio reduced glutathione/oxidized glutathione (p=0.0406) and total thiol levels (p=0.0166). Conclusion A low-protein diet during pregnancy and lactation is closely associated with increased oxidative stress and reduced antioxidant capacity in the hypothalamus of sixty-day-old rats.

RESUMO Objetivo Avaliar os efeitos da restrição proteica materna sobre o estresse oxidativo no hipotálamo de ratos de 60 dias de idade. Métodos Ratos Wistar machos foram divididos em dois grupos experimentais de acordo com a dieta da mãe durante a gestação e lactação: grupo controle (NP: 17% caseína n=6) e grupo desnutrido (LP: 8% caseína n=6). Aos 60 dias de vida, os ratos foram sacrificados para coleta do hipotálamo para posterior análise bioquímica. Resultados Os resultados demonstraram aumento do estresse oxidativo no grupo desnutrido, observado através do aumento do conteúdo de cabonilas (p=0,0357) e redução da atividade da enzima glutationa-S-transferase (p=0,0257) e da capacidade antioxidante não enzimática, evidenciada pela queda da razão glutationa reduzida/glutationa oxidada (p=0,0406) e dos níveis de tióis totais (p=0,0166). Conclusão Uma dieta com baixo teor de proteínas durante a gestação e lactação está intimamente associada ao aumento do estresse oxidativo e à redução da capacidade antioxidante no hipotálamo de ratos de 60 dias de vida.