Social-Single Prolonged Stress affects contextual fear conditioning in male and female Wistar rats: Molecular insights in the amygdala.

Stress exposure can lead to post-traumatic stress disorder (PTSD) in male and female rats. Social-Single Prolonged Stress (SPS) protocol has been considered a potential PTSD model. This study aimed to pharmacologically validate the Social-SPS as a PTSD model in male and female rats. Male and female Wistar rats (60-day-old) were exposed to Social-SPS protocol and treated with fluoxetine (10 mg/Kg) or saline solution intraperitoneally 24 h before euthanasia. Two cohorts of animals were used; for cohort 1, male and female rats were still undisturbed until day 7 post-Social-SPS exposure, underwent locomotor and conditioned fear behaviors, and were euthanized on day 9. Animals of cohort 2 were subjected to the same protocol but were re-exposed to contextual fear behavior on day 14. Results showed that fluoxetine-treated rats gained less body weight than control and Social-SPS in both sexes. Social-SPS effectively increased the freezing time in male and female rats on day eight but not on day fourteen. Fluoxetine blocked the increase of freezing in male and female rats on day 8. Different mechanisms for fear behavior were observed in males, such as Social-SPS increased levels of glucocorticoid receptors and Beclin-1 in the amygdala. Social-SPS was shown to increase the levels of NMDA2A, GluR-1, PSD-95, and CAMKII in the amygdala of female rats. No alterations were observed in the amygdala of rats on day fourteen. The study revealed that Social-SPS is a potential PTSD protocol applicable to both male and female rats.

Nucleophilic Selenocyclization Reaction of Benzodiynes Promoted by Sodium Selenide: Synthesis of Isoselenochromenes.

We describe here the synthesis of isoselenochromenes via a nucleophilic selenocyclization reaction of benzodiynes with sodium selenide. The central parameters that affect this cyclization reaction were studied, and the best reaction conditions were applied to different substrates to determine the scope of the method. The results indicated that isoselenochromenes were obtained in higher yields when the reactions were performed by the addition of NaBH4 (3 equiv), at room temperature, under nitrogen atmosphere, to a solution of elemental selenium (2 equiv) in dimethylformamide (2 mL). After 1 h, a benzodiynes (0.25 mmol) solution in EtOH (3 mL) was added at room temperature. The reaction was stirred at 75 °C until the starting material was consumed. The best conditions were applied to benzodiynes having electron-rich, electron poor aromatic rings, and alkyl groups directly bonded to the alkynes. The same reaction condition was extended to isothiochromene derivatives but failed to prepare isotelurochromenes. The isoselenochromenes were easily transformed into three new classes of organoselenium compounds using classical methods available in the literature. We also conducted several control experiments to propose a reaction mechanism.

Involvement of peripheral mast cells in a fibromyalgia model in mice.

Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT2A, 5-HT3, H1, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.

(p-ClPhSe)2 modulation on carbohydrate and lipid metabolism requires the insulin-like signaling in Caenorhabditis elegans.

Organoselenium compounds modulate the metabolism by regulating carbohydrate and lipid syntheses and degradation in the liver, muscle, and adipose tissue. Notably, p-chloro-diphenyl diselenide (p-ClPhSe)2 can directly regulate the activities of enzymes involved in glucose metabolism, suggesting an insulin-like effect in rodents; however, there is still a lack of scientific evidence to confirm this hypothesis. The objective of this study was to investigate (p-ClPhSe)2 effects on glucose and lipid metabolism in Caenorhabditis elegans. The contribution of AGE-1/PI3K, AKT-1, AKT-2, PFK-1, DAF-16, and DAF-2 in the (p-ClPhSe)2 effects were also investigated. Our results demonstrate that (p-ClPhSe)2 acute exposure presented some toxicity to the worms, and therefore, lower concentrations were further used. (p-ClPhSe)2 reduced glucose and triglyceride levels to the baseline levels, after induction with glucose or fructose, in wild-type worms. This effect required proteins involved in the insulin/IGF-1 like signaling, such as the DAF-2, AGE-1, AKT-1 and AKT-2, PFK-1, but also DAF-16, which would be negatively regulated by DAF-2 activation. Moreover, the reduction in glucose and triglyceride levels, caused by (p-ClPhSe)2per se was lost in age-1/daf-16 worms, suggesting that insulin/IGF-1-like signaling in a DAF-2 and AGE-1/DAF-16 dependent-manner in C. elegans are necessary to effects of (p-ClPhSe)2. In conclusion, (p-ClPhSe)2 requires proteins involved in the IIS pathway to modulate carbohydrate and lipid metabolism.

Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity.

Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. ß-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.

Subchronic exposure to Tamoxifen modulates the hippocampal BDNF/ERK/Akt/CREB pathway and impairs memory in intact female rats.

Tamoxifen (TAM), a Selective Estrogen Receptor Modulator (SERM), is commonly used to treat and prevent breast cancer. Memory impairment has been noticed in patients who experience hormone therapy in the case of TAM and other SERMs. Animal studies that mimic the TAM longer exposure effects are needed to better elucidate the adverse effects of continuous treatment in humans. This study evaluated the effects of TAM subchronic administration on the memory performance and hippocampal neural plasticity of intact female Wistar rats. Animals were treated intragastrically with TAM (0.25 and 2.5 mg/kg) for 59 days. The rats were subjected to the Object Location Test (OLT) and Object Recognition Test (ORT) to evaluate memory performance. After euthanasia, the hippocampus samples were excised and the protein levels of the BDNF/ERK/Akt/CREB pathway were evaluated. The rat's locomotor activity and hippocampal TrkB levels were similar among the experimental groups. TAM at both doses reduced the memory performance of female rats in the OLT and short-term memory of ORT, and impaired hippocampal levels of mBDNF, proBDNF, and pCREB/CREB. TAM only at the dose of 2.5 mg/kg reduced the memory performance of rats in the long-term memory of ORT and hippocampal pERK/ERK and pAkt/Akt ratios. TAM subchronic administration induced amnesic effects and modulated the hippocampal BDNF/ERK/Akt/CREB pathway in intact young adult female Wistar rats.

(m-CF3-PhSe)2 counteracts metabolic disturbances and hypothalamic inflammation in a lifestyle rodent model.

An unhealthy lifestyle is associated with metabolic disorders and neuroinflammation. In this study, the efficacy of m-trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] against lifestyle model-related metabolic disturbances and hypothalamic inflammation in young mice was investigated. From postnatal day 25 (PND25) to 66, male Swiss mice were subjected to a lifestyle model, an energy-dense diet (20:20% lard: corn syrup) and sporadic ethanol (3x/week). Ethanol was administrated intragastrically (i.g., 2 g/kg) to mice from PND45 to 60. From PND60 to 66, mice received (m-CF3-PhSe)2 (5 mg/kg/day; i. g). (m-CF3-PhSe)2 reduced relative abdominal adipose tissue weight, hyperglycemia, and dyslipidemia in mice exposed to the lifestyle-induced model. (m-CF3-PhSe)2 normalized hepatic cholesterol and triglyceride levels, and the activity of G-6-Pase increased in lifestyle-exposed mice. (m-CF3-PhSe)2 was effective in modulating hepatic glycogen levels, citrate synthase and hexokinase activities, protein levels of GLUT-2, p-IRS/IRS, p-AKT/AKT, redox homeostasis, and inflammatory profile of mice exposed to a lifestyle model. (m-CF3-PhSe)2 counteracted hypothalamic inflammation and the ghrelin receptor levels in mice exposed to the lifestyle model. (m-CF3-PhSe)2 reversed the decreased levels of GLUT-3, p-IRS/IRS, and the leptin receptor in the hypothalamus of lifestyle-exposed mice. In conclusion, (m-CF3-PhSe)2 counteracted metabolic disturbances and hypothalamic inflammation in young mice exposed to a lifestyle model.

Neuroprotective effect of Eugenia uniflora against intranasal MPTP-induced memory impairments in rats: The involvement of pro-BDNF/p75NTR pathway.

Parkinson's disease is a multisystemic neurodegenerative disorder that includes motor and non-motor symptoms, and common symptoms include memory loss and learning difficulties. Thus, we investigated the neuroprotective potential of a hydroalcoholic extract of Brazilian purple cherry (Eugenia uniflora) (HAE-BC) on memory impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats and the involvement of hippocampal BDNF/TrkB/p75NTR pathway in its effects. Adult male Wistar rats were exposed to MPTP (1 mg/nostril) or vehicle. Twenty-four hours later, the HAE-BC treatments began at doses of 300 or 2000 mg/kg/day or vehicle for 14 days. From 7 days after the MPTP induction, the animals were subjected to behavioral tests to evaluate several cognitive paradigms. HAE-BC treatments, at both doses, blocked the MPTP-caused disruption in the social recognition memory, short- and long-term object recognition memories, and working memory. Furthermore, MPTP-induced motor deficit linked to striatal tyrosine hydroxylase levels decreased, which was blocked by HAE-BC. Our findings demonstrated that HAE-BC blocked the MPTP-induced increase in the hippocampal pro-BDNF, TrkB.t1, and p75NTR levels. The pro-BDNF/p75NTR interaction negatively regulates synaptic transmission and plasticity, and the neuroprotective effect of HAE-BC was related, at least partly, to the modulation of this hippocampal signaling pathway. Thus, our study reports the first evidence of the potential therapeutic of E. uniflora in a Parkinson's disease model in rodents.

(m-CF3-PhSe)2 benefits against anxiety-like phenotype associated with synaptic plasticity impairment and NMDAR-mediated neurotoxicity in young mice exposed to a lifestyle model.

Lifestyle habits including energy-dense foods and ethanol intake are associated with anxiety disorders. m-Trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] has been reported to modulate serotonergic and opioidergic systems and elicit an anxiolytic-like phenotype in animal models. This study investigated if the modulation of synaptic plasticity and NMDAR-mediated neurotoxicity contributes to the (m-CF3-PhSe)2 anxiolytic-like effect in young mice exposed to a lifestyle model. Swiss male mice (25-days old) were subjected to a lifestyle model, an energy-dense diet (20:20% lard: corn syrup) from the postnatal day (PND) 25-66 and sporadic ethanol (2 g/kg) (3 x a week, intragastrically, i.g.) from PND 45 to 60. From PND 60 to 66, mice received (m-CF3-PhSe)2 (5 mg/kg/day; i.g). The corresponding vehicle (control) groups were carried out. After, mice performed anxiety-like behavioral tests. Mice exposed only to an energy-dense diet or sporadic ethanol did not show an anxiety-like phenotype. (m-CF3-PhSe)2 abolished the anxiety-like phenotype in young mice exposed to a lifestyle model. Anxious-like mice showed increased levels of cerebral cortical NMDAR2A and 2B, NLRP3 and inflammatory markers, and decreased contents of synaptophysin, PSD95, and TRκB/BDNF/CREB signaling. (m-CF3-PhSe)2 reversed cerebral cortical neurotoxicity, the increased levels of NMDA2A and 2B, and decreased levels of synaptic plasticity-related signaling in the cerebral cortex of young mice exposed to a lifestyle model. In conclusion, the (m-CF3-PhSe)2 anxiolytic-like effect was associated with the modulation of NMDAR-mediated neurotoxicity and synaptic plasticity in the cerebral cortex of young mice exposed to the lifestyle model.

Effectiveness of diphenyl diselenide against experimental sporotrichosis caused by Sporothrix brasiliensis.

Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (P < .001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.

We evaluated the activity of diphenyl diselenide (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. This is the first demonstration of the potential use of (PhSe)2, alone or in an association against sporotrichosis.

Emotional-Single Prolonged Stress: A promising model to illustrate the gut-brain interaction.

Excessive stress can precipitate depression and anxiety diseases, and damage gastrointestinal functionality and microbiota changes, favoring the development of functional gastrointestinal disorders (FGIDs) - defined by dysregulation in the brain-gut interaction. Therefore, the present study investigated if Emotional-Single Prolonged Stress (E-SPS) induces depressive/anxiety-like phenotype and gut dysfunction in adult Swiss male mice. For this, mice of the E-SPS group were subjected to three stressors sequential exposure: immobilization, swimming, and odor of the predator for 7 days (incubation period). Next, animals performed behavior tests and 24 h later, samples of feces, blood, and colon tissue were collected. E-SPS increased the plasma corticosterone levels, immobility time in the tail suspension and forced swim test, decreased the grooming time in the splash test, OAT%, and OAE% in the elevated plus-maze test, as well as increased anxiety index. Mice of E-SPS had increased % of intestinal transit rate, % of fecal moisture content, and fecal pellets number, and decreased Claudin1 content in the colon. E-SPS decreased the relative abundance of Bacteroidetes phylum, Bacteroidia class, Bacteroidales order, Muribaculaceae and Porphyromonadaceae family, Muribaculum, and Duncaniella genus. However, E-SPS increased Firmicutes and Actinobacteria phylum, Coriobacteriales order, and the ratio of Firmicutes/Bacteroidetes, and demonstrated Mucispirillum genus presence. The present study showed that E-SPS induced depressive/anxiety-like phenotype, predominant diarrhea gut dysfunction, and modulated the gut bacterial microbiota profile in male adult Swiss mice. E-SPS might be a promising model for future studies on the brain-gut interaction and the development of FGIDs with psychological comorbidities.

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.

Electrophile-Promoted Nucleophilic Cyclization of 2-Alkynylindoles to Give 4-Substituted Oxazinoindolones.

A method for the synthesis of 4-organoselanyl oxazinoindolone derivatives by the cascade cyclization of N-(alkoxycarbonyl)-2-alkynylindoles using iron(III) chloride and diorganyl diselenides as promoters was developed. This protocol was applied to a series of N-(alkoxycarbonyl)-2-alkynylindoles containing different substituents. The reaction conditions also tolerated a variety of diorganyl diselenides having both electron donating and electron withdrawing groups. However, the reaction did not work for diorganyl disulfides and ditellurides. The reaction mechanism seems to proceed via an ionic pathway and the cooperative action between iron(III) chloride and diorganyl diselenides is crucial for successful cyclization. We also found that using the same starting materials, by simply changing the electrophilic source to iodine, led to the formation of 4-iodo-oxazinoindolones. The high reactivity of Csp2 -Se and Csp2 -I bonds were tested under cross-coupling conditions leading to the preparation of a new class of functionalized indole derivatives. In addition, the absorption, emission and electrochemical properties of 4-organoselanyl oxazinoindolones showed an important relationship with the substituents of the aromatic rings. The advantages of the methodology include the use of electrophilic to promote the cyclization reaction and functionalization of the indole ring, and the electronic properties presented by the prepared compounds can be exploited as probes, analyte detectors and optical materials.

Potassium tert-Butoxide-Promoted Tandem Cyclization of Organoselenium Alkynyl Aryl Propargyl Ethers.

Base-promoted cyclization of 3-organoselenyl-methylene-2-alkynyl aryl propargyl ethers has been developed for the synthesis of 3-butylselanyl-methylene benzofurans, 3-methyl-2-alkynyl-benzofurans, and 4-iodo-benzo[b]furan-fused selenopyrans. Under potassium tert-butoxide as the base and tetrahydrofuran as the solvent, at room temperature, 3-organoselenyl-methylene-2-alkynyl aryl propargyl ethers were converted into 3-butylselanyl-methylene benzofurans via a 5-exo-dig mode. Using the same substrate, changing the solvent to dimethylsulfoxide, 3-methyl-2-alkynyl-benzofurans were selectively obtained in good yields. From 3-butylselanyl-methylene benzofurans, 4-iodo-benzo[b]furan-fused selenopyrans were prepared through a nucleophilic cyclization promoted by molecular iodine. The optimization of the reaction conditions showed that the solvents governed the regioselectivity of this cyclization and the initial formation of the dimsyl anion by the reaction of dimethylsulfoxide with potassium tert-butoxide was crucial for the 3-methyl-2-alkynyl-benzofuran preparation. We also proposed the mechanism for the formation of the products, demonstrated that the methodology can be scaled up, and showed the application of the prepared compounds as substrate in further transformations.

Locust Bean Gum Nano-Based Hydrogel for Vaginal Delivery of Diphenyl Diselenide in the Treatment of Trichomoniasis: Formulation Characterization and In Vitro Biological Evaluation.

Trichomoniasis is the most common nonviral sexually transmitted infection in the world, but its available therapies present low efficacy and high toxicity. Diphenyl diselenide (PhSe2) is a pharmacologically active organic selenium compound; however, its clinical use is hindered by its lipophilicity and toxicity. Nanocarriers are an interesting approach to overcome the limitations associated with this compound. This study designed and evaluated a vaginal hydrogel containing PhSe2-loaded Eudragit® RS100 and coconut oil nanocapsules for the treatment of trichomoniasis. Nanocapsules presented particle sizes in the nanometric range, positive zeta potential, a compound content close to the theoretical value, and high encapsulation efficiency. The nanoencapsulation maintained the anti-Trichomonas vaginalis action of the compound while improving the scavenger action in a DPPH assay. The hydrogels were prepared by thickening nanocapsule suspensions with locust bean gum (3%). The semisolids maintained the nanometric size of the particles and the PhSe2 content at around the initial concentration (1.0 mg/g). They also displayed non-Newtonian pseudo-plastic behavior and a highly mucoadhesive property. The chorioallantoic membrane method indicated the absence of hemorrhage, coagulation, or lysis. The compound, from both non-encapsulated and nano-based hydrogel delivery systems, remained on the surface of the bovine vaginal mucosa. Therefore, the formulations displayed the intended properties and could be a promising alternative for the treatment of trichomoniasis.

Stereoselective Reduction of Alkynes: Synthesis of 4-Organoselenyl Quinolines.

This study describes the reaction of 2-amino arylalkynyl ketones with organoselenolates to form (Z)-vinyl selenides, which lead to 4-organoselenyl quinolines via an intramolecular condensation. Using the optimized reaction conditions, the generality of this cyclization was studied with various arylalkynyl ketones and diorganyl diselenides. The study of the reaction mechanisms led to the isolation and identification of a vinyl selenide, which was the key intermediate for this cyclization. To expand the structural diversity and to demonstrate the applicability of the 4-organoselenyl quinolines prepared, we studied their application as substrates in the cleavage of the carbon-selenium bond using n-butyllithium followed by the capture of the lithium intermediate by electrophiles and Suzuki and Sonogashira cross-coupling reactions.

Nano-based formulations as an approach for providing a novel identity for organoselenium compounds.

The organoselenium compounds belong to a class of synthetic molecules that displays a remarkable spectrum of promising pharmacological properties. Despite the huge amount of preclinical data that supports a bright outlook for organoselenium compounds, some toxicity issues and physicochemical limitations delay the development of more advanced studies. Currently, several scientific reports demonstrated that the association of nanotechnology has emerged as an alternative to improve solubility and safety issues of these molecules as well as enhance pharmacological properties. Therefore, our main objective was to address studies that reported the development and biological evaluations of nano-based formulations to synthetic organoselenium compounds incorporation by constructing an integrative literature review. The data survey was performed using the Science Direct, PubMed, Web of Science, and SCOPUS online databases, covering studies that were published from January 2011 up to October 2021. In the last decade, there has been an exponential growth in research regarding the incorporation of synthetic organoselenium compounds into distinct nanocarrier systems such as nanocapsules, nanoemulsions, micelles, and others, reinforcing that the association of such molecules and nanotechnology is a promising alliance. The reports investigated many nanosystems containing selenium organic molecules intending oral, intravenous, and cutaneous applications. Besides that, these systems were evaluated in a variety of in vitro techniques and in vivo models, concerning their pharmacological potential, biodistribution profile, and safety. In summary, the findings indicate that the production of nano-based formulations containing organoselenium compounds either improved physicochemical and biological properties or minimize toxicological issues of compounds.

Social-single prolonged stress as an ether-free candidate animal model of post-traumatic stress disorder: Female and male outcomings.

BACKGROUND: Single Prolonged Stress (SPS) is a valid animal model that reflects the core of post-traumatic stress disorder (PTSD) phenotypes. Although SPS has been a pivotal tool, it can bring ethics approval difficulties due to the use of ether as a stressor. The present study evaluated if changing a chemical (ether) with a social stressor resembles the PTSD hallmark symptoms. METHODS: Female and male young adult rats were distributed in Sham and Social-SPS groups. Rats in Social-SPS groups were subjected to stress, whereas those in Sham groups remained undisturbed. One set of animals performed the behavioral tests, elevated plus-maze (EPM) and Y-maze. Plasma corticosterone levels and cortical and hippocampal molecular protein contents were analyzed. Another set of animals performed the dexamethasone suppression test. RESULTS: A significant decrease in the percentage of time spent and the number of entries in open arms and an increase in anxiety index in the EPM were observed in rats of the social-SPS groups. In the Social-SPS groups, rats reduced the spontaneous alternations in Y-maze. The Social-SPS exposure enhanced the HPA-axis feedback and increased glucocorticoid receptor contents in the cerebral cortex and hippocampus of rats. A decrease in the content of synaptic integrity-related proteins, synaptophysin, and PSD-95, were found in the cortex and hippocampus of rats subjected to social-SPS. There were no statistical differences between males and females in any parameter analyzed. LIMITATIONS: The absence of a task to recap criterion E 'arousal' and predictive validity experiments. CONCLUSIONS: This study reveals that social-SPS recapitulated the main clusters required for a candidate animal model of PTSD.

Impact of two different types of exercise training on AMPH addiction: Role of hippocampal neurotrophins.

INTRODUCTION: Amphetamine (AMPH) abuse results in neurobehavioral alterations related to the reward circuit. The hippocampus plays a role in cognition, reward, and drug addiction. There are no pharmacological approaches to prevent AMPH relapse. Physical exercise has been studied as a non-pharmacological promising influence to attenuate reward symptoms related to addictive drugs. OBJECTIVE: This study aimed to compare the effects of non-weight-loaded and weight-loaded physical exercise on behavioral (relapse, memory and anxiety) and hippocampal molecular parameters associated with AMPH addiction in Wistar rats. METHODS: Male rats were subjected to the AMPH-Conditioned Place Preference (CPP) paradigm. After 8-conditioning days, they were subjected to swimming physical exercise protocol (without or with weight-load). Behavioral evaluations were performed to assess the influence of both exercise protocols in addiction parameters, including relapse after AMPH reconditioning, working memory, locomotor activity, and anxiety-like symptoms. Subsequently, protein levels of Brain-Derived Neurotrophic Factor (BDNF) and pro-BDNF ex-vivo assays were carried out in samples of the hippocampus of the animals. RESULTS: AMPH relapse and anxiety-like behaviors were reduced only in rats subjected to non-weight-loaded exercise. Hippocampal BDNF and pro-BDNF immunoreactivity were increased in non-weight-loaded exercise rats. Behavioral and molecular analyses were not modified in rats subjected to weight-loaded exercise. CONCLUSION: These findings demonstrate that non-weight-loaded exercise was more effective against relapse and anxiety-like behavior induced by AMPH. Non-weight-loaded exercise upregulated the hippocampal immunocontent levels in rats.

p-Chloro-diphenyl diselenide modulates Nrf2/Keap1 signaling and counteracts renal oxidative stress in mice exposed to repeated dexamethasone administrations.

Dexamethasone is a synthetic glucocorticoid that has been associated with oxidative stress in central and peripheral tissues. p-Chloro-diphenyl diselenide ((p-ClPhSe)2) is an antioxidant organoselenium compound. The present study evaluated whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1) signaling contributes to the (p-ClPhSe)2 antioxidant effects in the kidney of mice exposed to dexamethasone. Adult Swiss mice received dexamethasone (intraperitoneal) at a dose of 2 mg/kg or its vehicle for 21 days. After that, mice were treated with (p-ClPhSe)2 (intragastric) (1, 5, or 10 mg/kg) for 7 days. Samples of kidneys were collected for biochemical assays. (p-ClPhSe)2 at a dose of 1 mg/kg reversed the renal reactive oxygen species (ROS) and carbonyl protein (CP) levels increased by dexamethasone. (p-ClPhSe)2 at doses of 5 and 10 mg/kg was effective against the increase of thiobarbituric acid reactive substances, ROS, and CP, as well as the decrease of δ-aminolevulinic acid dehydratase activity and nonprotein sulfhydryl levels induced by dexamethasone. At 5 mg/kg, (p-ClPhSe)2 reduced the renal levels of 4-OH-2-HNE and heme oxygenase (HO-1), as well as modulated the Nrf2/Keap-1 signaling in mice exposed to dexamethasone. The present findings revealed that (p-ClPhSe)2 antioxidant effects were associated with the modulation of Nrf2/Keap-1 signaling pathway in the kidney of mice exposed to dexamethasone.