Resistance Training Modulates Hippocampal Neuroinflammation and Protects Anxiety-Depression-like Dyad Induced by an Emotional Single Prolonged Stress Model.

Stress is a triggering factor for anxious and depressive phenotypes. Exercise is known for its action on the central nervous system. This study aimed to evaluate the role of resistance exercise in an anxiety-depression-like dyad in a model of stress. Male Swiss mice (35-day-old) were exercised, three times a week for 4 weeks on nonconsecutive days. The resistance exercise consisted of climbing a 1-m-high ladder 15 times. After mice were subjected to an emotional single prolonged stress (Esps) protocol. Seven days later, they were subjected to anxiety and depression predictive behavioral tests. The results showed that exercised mice gain less weight than sedentary from weeks 3 to 5. Resistance exercise was effective against an increase in immobility time in the forced swim test and tail suspension test and a decrease in grooming time of mice subjected to Esps. Resistance exercise protected against the decrease in the percentage of open arms time and open arm entries, and the increase in the anxiety index in Esps mice. Four-week resistance exercise did not elicit an antidepressant/anxiolytic phenotype in non-stressed mice. Esps did not alter plasma corticosterone levels but increased the hippocampal glucocorticoid receptor content in mice. Resistance exercise protected against the decrease in hippocampal levels of tropomyosin kinase B (TRκB), the p-Akt/Akt, and the p-mTOR/mTOR ratios of Esps mice. Resistance exercise proved to be effective in decreasing hippocampal neuroinflammation in Esps mice. Resistance exercise protected against the increase in the hippocampal Akt/mTOR pathway and neuroinflammation, and anxiety/depression-like dyad in Esps exposed mice.

Enhanced pharmacological actions of p,p'-methoxyl-diphenyl diselenide-loaded polymeric nanocapsules in a mouse model of neuropathic pain: Behavioral and molecular insights.

Neuropathic pain is a public health problem and its treatment is a global challenge. The organoselenium compound p,p'-methoxyl-diphenyl diselenide [(OMePhSe)2] has a potential antinociceptive action and its incorporation into nanocapsules improves this action. The current study evaluated if (OMePhSe)2 administration, free or incorporated into nanocapsules, reduces the chronic pain-like behavior induced by the partial sciatic nerve ligation (PSNL) surgery, a neuropathic pain mouse model. It was also investigated the (OMePhSe)2 restorative effect against the increase in inflammatory and apoptotic protein contents at the central nervous system caused by PSNL to mice. Male Swiss mice were subjected to PSNL during 4 weeks and treated with (OMePhSe)2, free or incorporated into nanocapsules, in a single (25mg/kg, i.g.) or repeated administration schedule (25mg/kg, i.g., once a day for seven days). Both treatments reduced mechanical hypernociception induced by PSNL, but the nanoencapsulation increased the (OMePhSe)2 antinociceptive action two-fold in comparison to its free form. PSNL increased the inflammatory protein contents (iNOS, COX-2, NF-κB, IL-1ß and TNF-α) and those of bax and clivated PARP, and reduced bcl-2 content, apoptotic proteins, in the mouse cerebral contral lateral cortex. Furthermore, PSNL induced an activation of MAPK pathway (ERK1,2 and p38). The free or nanoencapsulated (OMePhSe)2 repeated administration restored the molecular changes in the protein contents. This study demonstrates the (OMePhSe)2 nanocapsule effectiveness in an animal model of chronic pain.

Pomegranate seed oil nanoemulsions improve the photostability and in vivo antinociceptive effect of a non-steroidal anti-inflammatory drug.

The combination of pomegranate seed oil and ketoprofen in nanoemulsions aiming to improve the antinociceptive effect was evaluated according to the writhing test and Complete Freud's Adjuvant induced paw inflammation in mice. The formulations showed adequate characteristics and improved ketoprofen's photostability against UVC radiation exposure. The dialysis bag technique showed that 100% of the drug was released from the nanoemulsions after 3h and the oil amount had no influence on the releasing. Furthermore, time- and dose-response curves were obtained to determine the antinociceptive effect of the formulations. In the post-test, the nanoemulsion containing ketoprofen significantly reduced abdominal constrictions in time-response curve, showing effect up to 12h while the free ketoprofen showed effect up to 3h. In addition, the blank nanoemulsion presented a reduction of abdominal constriction up to 1h of pre-treatment. Regarding the dose-response curve, the free ketoprofen presents effect at 0.5mg/Kg dose and nanoemulsion at 1.0mg/Kg dose. Time- and dose-response curves were performed to determine the antinociceptive effect in inflammatory pain. After the evaluation of mechanical allodynia testing at the Von Frey Hair, the free ketoprofen showed effect up to 6h while nanoemulsions presented effect up to 10h. Moreover, acute toxicity was performed with ALT and AST activity evaluations and urea levels. After 7 days of treatment, no toxic effects for nanoemulsions were found. In conclusion, ketoprofen-loaded pomegranate seed oil nanoemulsions presented adequate characteristics and a high antinociceptive activity in the animal models tested.

Depression-related behavior and mechanical allodynia are blocked by 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene in a mouse model of neuropathic pain induced by partial sciatic nerve ligation.

Clinically, it is suggested that chronic pain might induce mood disorders like depression and anxiety. Based on this antidepressant drugs have emerged as a new therapy for pain. In this study, the effect of acute and subchronic treatments with 3-(4-fluorophenylselenyl)-2,5-diphenylselenophene (F-DPS) on behavioral changes induced by partial sciatic nerve ligation (PSNL) was evaluated. At the 4th week after surgery, PSNL caused a significant depression-like behavior in mice evaluated in the forced swimming test (FST) and the tail suspension test (TST), which was accompanied by increased pain sensitivity. The anxiety-like behavior assessed in the light-dark test (LDT) was not modified by PSNL. Acute treatment with F-DPS, at a dose of 1 mg/kg, intragastrically (i.g.) administered 30 min before the FST, produced a significant anti-immobility effect in PSNL mice. The antidepressant drug paroxetine showed acute antidepressant-like action at a dose 10 times higher than F-DPS. Subchronic treatment with F-DPS (0.1 mg/kg, i.g.) reversed depression-like behavior of sciatic nerve-ligated mice in the TST and FST and produced a significant anxiolytic-like action in both sham-operated and PSNL animals. Although the acute F-DPS treatment did not produce anti-allodynic effect, F-DPS subchronic treatment significantly reduced pain sensitivity in PSNL mice. These findings demonstrated that F-DPS blocked behavioral changes induced by neuropathic pain, suggesting that it might be attractive in the pharmacological approach of pain-emotion diseases.