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Introduction: Obesity is usually triggered by a nutrient overload that favors adipocyte hypertrophy and increases the number of pro-inflammatory cells and mediators into adipose tissue. These mediators may be regulated by suppressors of cytokine signaling (SOCS), such as SOCS2, which is involved in the regulation of the inflammatory response of many diseases, but its role in obesity is not yet known. We aimed to investigate the role of SOCS2 in metabolic and inflammatory dysfunction induced by a high-refined carbohydrate-containing diet (HC)., Material and Methods: Male C57BL/6 wild type (WT) and SOCS2 deficient (SOCS2 -/- ) mice were fed chow or an HC diet for 8 weeks., Results: In general, SOCS2 deficient mice, independent of the diet, showed higher adipose tissue mass compared with their WT counterparts that were associated with decreased lipogenesis rate in adipose tissue, lipolysis in adipocyte culture and energy expenditure. An anti-inflammatory profile was observed in adipose tissue of SOCS2 -/- by reduced secretion of cytokines, such as TNF and IL-6, and increased M2-like macrophages and regulatory T cells compared with WT mice. Also, SOCS2 deficiency reduced the differentiation/expansion of pro-inflammatory cells in the spleen but increased Th2 and Treg cells compared with their WT counterparts., Conclusion: The SOCS2 protein is an important modulator of obesity that regulates the metabolic pathways related to adipocyte size. Additionally, SOCS2 is an inflammatory regulator that appears to be essential for controlling the release of cytokines and the differentiation/recruitment of cells into adipose tissue during the development of obesity., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Malaria, parasitic disease considered a major health public problem, is caused by Plasmodium protozoan genus and transmitted by the bite of infected female Anopheles mosquito genus. Cerebral malaria (CM) is the most severe presentation of malaria, caused by P. falciparum and responsible for high mortality and enduring development of cognitive deficits which may persist even after cure and cessation of therapy. In the present study we evaluated selected behavioral, neurochemical and neuropathologic parameters after rescue from experimental cerebral malaria caused by P. berghei ANKA in C57BL/6 mice. Behavioral tests showed impaired nest building activity as well as increased marble burying, indicating that natural behavior of mice remains altered even after cure of infection. Regarding the neurochemical data, we found decreased α2/α3 Na + ,K + -ATPase activity and increased immunoreactivity of phosphorylated Na + ,K + -ATPase at Ser 943 in cerebral cortex after CM. In addition, [ 3 H]-Flunitrazepam binding assays revealed a decrease of benzodiazepine/GABA A receptor binding sites in infected animals. Moreover, in hippocampus, dot blot analysis revealed increased levels of protein carbonyls, suggesting occurrence of oxidative damage to proteins. Interestingly, no changes in the neuropathological markers Fluoro-Jade C, Timm staining or IBA-1 were detected. Altogether, present data indicate that behavioral and neurochemical alterations persist even after parasitemia clearance and CM recovery, which agrees with available clinical findings. Some of the molecular mechanisms reported in the present study may underlie the behavioral changes and increased seizure susceptibility that persist after recovery from CM and may help in the future development of therapeutic strategies for CM sequelae., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Cognitive dysfunction is a major sign of cerebral malaria (CM). However, the underlying mechanisms of CM cognitive outcome remain poorly understood. A body of evidence suggests that adult neurogenesis may play a role in learning and memory processes. It has also been reported that these phenomena can be regulated by the immune system. We hypothesized that memory dysfunction in CM results from hippocampal neurogenesis impairment mediated by the deregulated immune response during the acute phase of CM. C57Bl/6 mice were infected with Plasmodium berghei ANKA (PbA) strain, using a standardized inoculation of 10(6) parasitized erythrocytes. Long-term working memory was evaluated using the novel object recognition test. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-receptor-kinase (TRK-B) and nerve growth factor (NGF) in the frontal cortex and hippocampus was estimated by real-time polymerase chain reaction (PCR). The protein levels of cytokine interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and CCL11 and neurotrophins BDNF and NGF were determined using a cytometric bead array (CBA) kit or enzyme-linked immunosorbent assay. Cell viability in the hippocampus was analyzed by Confocal Microscopy. Neurogenesis in the dentate gyrus was determined through quantification of doublecortin (DCX) positive cells. PbA-infected mice presented working memory impairment on day 5 post-infection. At this same time point, CM mice exhibited a decrease in DCX-positive cells in the dentate gyrus in parallel with increased cell death and elevated inflammatory cytokines (IL-6, TNF-α, IFN-γ and CCL11) in the hippocampus and frontal cortex. A significant reduction of BDNF mRNA expression was also found. IL-6 and TNF-α correlated negatively with BDNF and NGF levels in the hippocampus of CM mice. In summary, we provide further evidence that neuroinflammation following PbA-infection influences neurotrophin expression, impairs adult hippocampal neurogenesis and increases hippocampal cell death in association with memory impairment following CM course. The current study identified potential mediators of memory impairment in CM., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)