Intranasal administration of interleukin-4 ameliorates depression-like behavior and biochemical alterations in mouse submitted to the chronic unpredictable mild stress: modulation of neuroinflammation and oxidative stress.

Physical and psychological stress modulates the hypothalamic pituitary adrenal (HPA) axis, and the redox and inflammatory systems. Impairments in these systems have been extensively reported in major depression (MD) patients. Therefore, our study aimed to investigate the effects of the intranasal administration of interleukin-4 (IL-4) in mice with depressive-like behavior induced by chronic unpredictable mild stress (CUMS) for 28 days. On the 28th day, mice received IL-4 intranasally (1 ng/mouse) or vehicle (sterile saline), and after 30 min, they were submitted to behavioral tests or euthanasia for blood collection and removal of the adrenal glands, axillary lymph nodes, spleen, thymus, prefrontal cortices (PFC), and hippocampi (HC). A single administration of IL-4 reversed CUMS-induced depression-like behavior in the tail suspension test and splash test, without evoking locomotor changes. IL-4 administration reduced the plasma levels of corticosterone and the increased weight of suprarenal glands in stressed mice. Moreover, IL-4 restored the expression of nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor kappa B (NF-kB), interleukin 1 beta (IL-1ß), IL-4, brain derived neurotrophic factor (BDNF), and indoleamine 2,3-dioxygenase (IDO) in the PFC and HC and modulated oxidative stress markers in these brain structures in stressed mice. Our results showed for the first time the antidepressant-like effect of IL-4 through the modulation of neuroinflammation and oxidative stress. The potential effect of IL-4 administered intranasally arises as an innovative strategy for MD treatment.

A systematic review about biological control of phytopathogenic Phytophthora cinnamomi.

The oomycetes of the genus Phytophthora have the most aggressive species for agriculture and forestry, such as Phytophthora sojae which is responsible for soybean root rot, Phytophthora infestans responsible for the potato downy mildew that caused the diaspora in Ireland in the nineteenth-century, and Phytophthora cinnamomi that affects a wide variety of tree species, from avocado in America, trees in Oceania to European chestnut trees. P. cinnamomi reproduces either sexually or asexually and asexual zoospores can live as saprotrophs and subsist in the soil long after death and removal of host plants. Controlling this organism is very challenging for researchers due to the limited range of effective chemical inhibitors. In this work, we present a systematic review of alternatives for biocontrol of Phytophthora in general and P. cinnamomi in particular. Our literature review indicates that Trichoderma spp., mainly Trichoderma harzianum, T. virens, and T. asperellum are very promising fungal species in the control of different Phytophthora spp. The Bacillus genus is also very promising in the control and inhibition of several Phytophthoras spp.

Phytopathogenic oomycetes: a review focusing on Phytophthora cinnamomi and biotechnological approaches.

The Phytophthora genus is composed, mainly, of plant pathogens. This genus belongs to the Oomycete class, also known as "pseudo-fungi", within the Chromista Kingdom. Phytophthora spp. is highlighted due to the significant plant diseases that they cause, which represents some of the most economically and cultural losses, such as European chestnut ink disease, which is caused by P. cinnamomi. Currently, there have been four genome assemblies placed at the National Center for Biotechnology Information (NCBI), although the progress to understand and elucidate the pathogenic process of P. cinnamomi by its genome is progressing slowly. In this review paper, we aim to report and discuss the recent findings related to P. cinnamomi and its genomic information. Our research is based on paper databases that reported probable functions to P. cinnamomi proteins using sequence alignments, bioinformatics, and biotechnology approaches. Some of these proteins studied have functions that are proposed to be involved in the asexual sporulation and zoosporogenesis leading to the host colonization and consequently associated with pathogenicity. Some remarkable genes and proteins discussed here are related to oospore development, inhibition of sporangium formation and cleavage, inhibition of flagellar assembly, blockage of cyst germination and hyphal extension, and biofilm proteins. Lastly, we report some biotechnological approaches using biological control, studies with genome sequencing of P. cinnamomi resistant plants, and gene silencing through RNA interference (iRNA).

Depression-like behavior, hyperglycemia, oxidative stress, and neuroinflammation presented in diabetic mice are reversed by the administration of 1-methyl-3-(phenylselanyl)-1H-indole.

Oxidative stress and neuroinflammation are found both in diabetes mellitus and major depressive disorder (MDD). In addition to damage in peripheral organs, such as liver and kidney, diabetic patients have a higher risk of developing depression. In this sense, the objective of the present study was to characterize the antidepressant-like effect of a selenium-containing compound, the 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI), in streptozotocin (STZ)-induced diabetic mice. STZ (200 mg/kg, i.p.) was used to induce diabetes mellitus type I, and after seven days, the administration of MFSeI (10 mg/kg, i.g.) was initiated and followed for the next 14 days. Twenty-four hours after the last administration of MFSeI, the behavioral tests were performed, followed by euthanasia. The treatment with MFSeI was able to reverse the hyperglycemia induced by STZ. MFSeI also decreased the plasma levels of biomarkers of liver and kidney damage. Importantly, MFSeI reversed the depression-like behavior induced by STZ in the tail suspension test and forced swimming test without promoting locomotor alterations. Furthermore, MFSeI reversed the increased levels of reactive species and lipid peroxidation in the prefrontal cortex (PFC), hippocampus (HC), liver, and kidney of STZ-treated mice. Treatment with MFSeI also decreased the expression of tumor necrosis factor-alpha, inducible nitric oxide synthase and indoleamine 2,3-dioxygenase, while increasing the expression of interleukin-10, insulin receptor substrate-1 and glucose transport-4 in the PFC and HC of mice. Taken together, the results indicate the effectiveness of MFSeI against depression-like behavior and central and peripheral complications caused by diabetes in mice.

Depression- and anxiogenic-like behaviors induced by lipopolysaccharide in mice are reversed by a selenium-containing indolyl compound: Behavioral, neurochemical and computational insights involving the serotonergic system.

Major depression and anxiety are highly incapacitating psychiatric disorders often present simultaneously, and the causal relationship between these disorders and inflammation are under extensive investigation. The treatment for this comorbidity still relies on drugs acting on the serotonergic neurotransmission, but the modulation of immune-inflammatory pathways has attained an increasing interest in the drug discovery. We have previously demonstrated that the selenoorganic compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) possess antioxidant, anti-inflammatory, antinociceptive and antidepressant-like effect in mice. Considering these pharmacological properties and the structural similarities between tryptophan, serotonin and CMI, the aim of the present study was to investigate whether CMI ameliorates depression- and anxiogenic-like behavior induced by lipopolysaccharide (LPS) in Swiss male mice by modulating the serotonergic system and reducing neuroinflammation. The administration of CMI (1 mg/kg, i.g) reversed the behavioral deficits induced by LPS (0.83 mg/kg, i.p) in the tail suspension test, splash test and elevated plus maze. The pre-treatment of mice with WAY100635 (5-HT1A receptor antagonist), ketanserin (5-HT2A/2C receptor antagonist) and ondansetron (5-HT3 receptor antagonist) prevented the antidepressant- and anxiolytic-like effect elicited by CMI treatment after the LPS challenge. The administration of CMI also counteracted the increased expression of pro-inflammatory cytokines and indoleamine 2,3-dioxygenase (IDO) in the prefrontal cortex and hippocampus of mice challenged with LPS. Additionally, a molecular docking analysis showed that CMI binds to the active site of the serotonin transporter and IDO. These findings suggest that CMI reversed behavioral and biochemical alterations in the depression-anxiety comorbidity induced by LPS, possibly by modulation of neuroinflammatory mediators and the serotonergic system.

The selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole reverses depressive-like behavior induced by acute restraint stress in mice: modulation of oxido-nitrosative stress and inflammatory pathway.

RATIONALE AND OBJECTIVES: Stress-induced alterations in oxidative and inflammatory parameters have been implicated in the pathophysiology of mood disorders. Based on the antioxidant and anti-inflammatory properties of the selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI), we assessed its ability to reverse depression-like behavioral alterations, neuroinflammation, and oxidative imbalance induced by acute restraint stress. METHODS: Mice submitted to restraint for 240 min received CMI (1 or 10 mg/kg, orally) 10 min after the end of the stress induction. Behavioral and biochemical tests were carried out after further 30 min. RESULTS: Restraint-induced depression-like behavior in the tail suspension test (TST), splash test, and new object exploration test was reversed by CMI. None of the treatments evoked locomotor alteration. In addition, CMI abrogated restraint-induced increases in plasma levels of corticosterone and in markers of oxidative stress and impaired superoxide dismutase and catalase activity in the prefrontal cortex (PFC) and hippocampus (HC). CMI also blocked stress-induced downregulation of mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor and upregulation of nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis alpha, indoelamine-2,3-dioxygenase, and glycogen synthase kinase 3 beta in PFC and HC. CONCLUSIONS: These preclinical results indicate that administration of selenium-containing compounds might help to treat depression associated with inflammation and oxidative stress. Graphical abstract ᅟ.