Neuroprotective and Antioxidant Effects of Riparin I in a Model of Depression Induced by Corticosterone in Female Mice

Abstract

<b><i>Background:</i></b> Depression is a common, chronic, and often recurrent serious mood disorder. Conventional antidepressants present limitations that stimulate the search for new drugs. Antioxidant and neuroprotective substances are potential antidepressant agents. In this context, riparin I (RIP I) has presented promising results, emerging as a potential source of a new therapeutic drug. In this study, the antidepressant effect of RIP I was evaluated in an animal model of depression induced by corticosterone (CORT). The involvement of neuroprotective and antioxidant mechanisms in the generation of this effect was also assessed. <b><i>Methods:</i></b> Female mice were submitted to CORT for 21 days and treated with RIP I in the last 7 days. Behavioral and neurochemical analyses were performed. <b><i>Results:</i></b> The administration of RIP I reversed the depressive and psychotic-like behavior, as well as the cognitive impairment caused by CORT, in addition to regulating oxidative stress parameters and BDNF levels in depression-related brain areas. <b><i>Conclusion:</i></b> These findings suggest that RIP I can be a strong candidate for drugs in the treatment of depression.

Antidepressant-like effect of riparin I and riparin II against CUMS-induced neuroinflammation via astrocytes and microglia modulation in mice

“…Previous studies, using acute and chronic models of stress by repeated administration of corticosterone, have already demonstrated the ability of RIP I and RIP II to decrease the immobility time in forced swimming test, which proves their antidepressant activity (Teixeira et al, 2013;de Sousa et al, 2014;Lopes et al, 2018;Maia Oliveira et al, 2021). Additionally, in the present study, after exposure to various stressors in the CUMS, which is known to affect several brain circuits, resulting in the animal's immobility behavior (Nollet, 2021), RIP I and RIP II showed the ability to reverse the despair-like behavior caused by CUMS.…”

“…In previous studies from our group using acute animal models, RIP I and RIP II showed antidepressant and anxiolytic activities and the mechanism may be related to noradrenergic (α1 and α2 receptors), serotonergic (5-HT2A/2C receptor), and dopaminergic (D1 and D2 receptors) systems (de Sousa et al, 2005(de Sousa et al, , 2007(de Sousa et al, , 2014Teixeira et al, 2013). Furthermore, these molecules showed restorative properties on brain-derived neurotrophic factor (BDNF) levels, in addition to reducing oxidative stress damage in a model of depression induced by repeated administration of corticosterone in mice (Lopes et al, 2018;Maia Oliveira et al, 2021). In this study, we advance the model used to induce depression and cognitive impairments, more closely imitating what occurs in humans, employing a stress model with external factors rather than synthetic hormones (Antoniuk et al, 2019).…”

Prednisolone Targets Claudins in Mouse Brain Blood Vessels

“…Recent studies demonstrated the association between BBB disruption based on changes in the TJ proteins of the cerebral vascular endothelium and the development of psychiatric disorders, with claudin-5 and -12 being considered as the main targets [ 14 , 15 ]. Glucocorticoid treatment is known to induce depressive behavior in mice [ 26 , 27 , 28 ]. In this study, the administration of prednisolone caused decreased locomotor activity and anxiety-like and depression-like behavior; intriguingly, this occurred without changes in the expression of claudin-5 and -12.…”

“…All behavioral observations revealed significant changes in accordance with the effects of the application (vehicle) and prednisolone, respectively. The behavioral changes in the conditions of intraperitoneal administration of prednisolone (70 mg/kg) for 7 days (Figure 2) were also characteristic of the systemic action of glucocorticoids [26][27][28]. Although the subsequent molecular analyses focused on approaches with intramuscular injection, this subset was chosen to exclude any peripheral muscular effects during the behavioral analyses.…”

Essential oil from the roots of Paeonia lactiflora pall. has protective effect against corticosterone-induced depression in mice via modulation of PI3K/Akt signaling pathway

“…In addition, the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the regulation of cortisol, and it is also found that changes in HPA axis with increased amount of plasma cortisol is one of the biological features in severe depression patients (Keller et al, 2017;Malhi and Mann, 2018). For investigation of the depression, corticosterone (CORT) is commonly used to induce chronic depression animals with disorders in HPA axis function with high levels of cortisol and glucocorticoids in blood plasm which are similar to the patients with depression (Malhi and Mann, 2018;Zhou et al, 2021;Oliveira et al, 2022). In our present study, we have successfully prepared the depression mice with CORT injection (i.p.…”