Curcumin-Loaded Nanocapsules Reverses the Depressant-Like Behavior and Oxidative Stress Induced by ß-Amyloid in Mice.

Alzheimer's disease (AD) is a neurodegenerative disorder classically characterized by cognitive functions impairment. However, its symptomatology is complex and the depression is one of the most frequent behavioral changes in AD. AD pathology includes neuroinflammation and oxidative stress resulting in the Aß protein accumulation. Curcumin is a natural phenolic compound that shows antioxidant and anti-inflammatory properties. Nevertheless, therapeutic use of curcumin is limited due to its low bioavailability and biodistribution. In this context, the use of curcumin-loaded nanocapsules (NLC C) emerges to overcome its limitations. Thus, the present study investigated the effects of NLC C on the depressant-like behavior and oxidative stress induced by an animal model of AD. For this, Swiss male mice were divided into five groups. The Aß, Aß + NLC C and Aß + Curcumin groups received Aß25-35 aggregate (3 nmol/3 µL, i.c.v.). Control and NLC C groups received only vehicle. The NLC C were administered via gavage at a dose of 10 mg/kg in alternate days for 12 days. Our results demonstrated that Aß infusion induced a depressantant-like behavior observed in the tail suspension and forced swimming tests, which was reversed by NLC C treatment. No change was observed in mice locomotion. Furthermore, NLC C reduced the Aß-generated oxidative stress in the prefrontal cortex, evidenced by the increase in the reactive species levels, superoxide dismutase and catalase activities. Importantly, NLC C were more effective than the free curcumin. Thus, we demonstrated the antidepressant-like and antioxidant effects of NLC C in a mouse model of AD, suggesting its therapeutic potential for this disorder.

Effects of diphenyl diselenide on depressive-like behavior in ovariectomized mice submitted to subchronic stress: involvement of the serotonergic system.

RATIONALE: The transition to menopause is associated with an increased risk of depressed mood. OBJECTIVES: This study was conducted to investigate whether diphenyl diselenide [(PhSe)2] treatment could reduce the effects of postmenopausal depression-like behavior in ovariectomized female mice submitted to subchronic stress exposure. METHODS: Mice were divided into four groups: sham, (PhSe)2, ovariectomy (OVX), and OVX + (PhSe)2. Animals were ovariectomized/sham-operated and subjected to stress session once a day for 7 days from the fifth to the 11th day after OVX. The behavioral tests (open field, tail suspension (TST), and forced swimming (FST)) were performed on the 14th day after OVX. Mice were treated orally once a day with vehicle (canola oil, 10 ml/kg) or (PhSe)2 (10 mg/kg; 10 ml/kg) 30 min before being exposed to subchronic stress, or from the 11th to the 14th day. Paroxetine (8 mg/kg i.p.) and pargyline (30 mg/kg i.p.) were used as positive controls. The involvement of serotonergic receptor subtypes in the antidepressant-like effect of (PhSe)2 was assessed in the FST using WAY 100635 (0.1 mg/kg s.c.), ritanserin (1 mg/kg i.p.), and ondansetron (1 mg/kg i.p.) as serotonergic antagonists. Monoamine oxidase (MAO) A and B activities were also determined. RESULTS: The prolongation of immobility time in TST and FST in OVX mice submitted to subchronic stress was prevented by (PhSe)2 treatment. Ritanserin and ondansetron blocked the antidepressive-like effect of (PhSe)2, suggesting the involvement of 5-HT(2A/2C) and 5-HT3 receptor subtypes. Both paroxetine and pargyline were effective in reducing the immobility time of stressed OVX mice in the FST. No alterations in locomotor activity were observed. Although (PhSe)2 had inhibited in vitro MAO-A and MAO-B activities, none of the groups presented alterations neither in ex vivo MAO-A nor in MAO-B activity. CONCLUSIONS: (PhSe)2 treatment could influence mood and behavior, indicating a promising role of this organoselenium compound in the management of postmenopausal depressive symptoms.