Abstract
Background: This study aimed to investigate the antidepressant-like effect of lactate and elucidate its mechanisms in ovariectomized rats with repeated stress. Methods: Two experiments were conducted on female rats in which all groups, except normal, were ovariectomized and underwent immobilization for 14 days. Lactate was administered orally (100, 250, and 500 mg/kg) for 14 consecutive days, and the rats’ cutaneous body temperature was measured during the same period. Depression-like behavior in rats was assessed by the tail suspension test (TST) and forced swimming test (FST). Furthermore, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were conducted to evaluate the changes that occurred in the neurotransmitter levels and activity. Results: The lactate 100 and 250 groups had reduced time spent immobile in TST and FST and decreased peripheral body temperature. In ELISA tests, the lactate 250 group expressed elevated levels of serotonin and dopamine in many brain areas. Tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and protein kinase C (PKC) immunoreactive cells showed increased density and cell counts in lactate administered groups. Conclusion: Results indicated that lactate has an antidepressant effect that is achieved by activation of PKC and upregulation of TH and TPH expression, which eventually leads to enhanced serotonin and dopamine levels in the menopausal rat’s brain.
Highlights
The World Health Organization recently published a report indicating that major depressive disorders (MDD) are affecting 322 million people all around the world, and the prevalence among women is higher than in men by one and a half to three times
We aimed to investigate the antidepressant-like effect of lactate and elucidate its mechanisms in ovariectomized and repeatedly stressed female rats
No previous study or literature reviews showed the effects of oral lactate biosensor in the hippocampus, and did not produce any significant effect on locomotor activity and administration in the modulation of monoaminergic neurotransmitters or in improving depression neuromuscular strength
Summary
The World Health Organization recently published a report indicating that major depressive disorders (MDD) are affecting 322 million people all around the world, and the prevalence among women is higher than in men by one and a half to three times. Numerous researchers have tried to explain the pathophysiology of menopausal depression by estrogen withdrawal theory. This theory suggests that diminished estrogen levels affect brain neurotransmitters, such as dopamine, norepinephrine, and serotonin [2,3]. This study aimed to investigate the antidepressant-like effect of lactate and elucidate its mechanisms in ovariectomized rats with repeated stress. Methods: Two experiments were conducted on female rats in which all groups, except normal, were ovariectomized and underwent immobilization for 14 days. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were conducted to evaluate the changes that occurred in the neurotransmitter levels and activity
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