Balancing the immune response in the brain: IL-10 and its regulation

Background: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. Main body: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders. Conclusion: The regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to DLS (SFRH/BD/88081/2012) and a post-doctoral fellowship to SR (SFRH/BPD/72710/2010). DS, AGC and SR were funded by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and National Funds through FCT under the scope of the project POCI-01-0145-FEDER007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The MS lab was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences ” (POCI-01-0145-FEDER-007274). MS is a FCT Associate Investigator. The funding body had no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript

Long-term administration of Greek Royal Jelly improves spatial memory and influences the concentration of brain neurotransmitters in naturally aged Wistar male rats

Ethnopharmacological relevance Royal Jelly (RJ) is a bee-derived product that has been traditionally used in the European and Asian systems of medicine for longevity. RJ has various pharmacological activities that may prevent aging e.g., anti-inflammatory, anti-oxidative, anti-hypercholesterolemic and anti-hyperglycemic properties. Aim of the study To evaluate the behavioral and neurochemical effects of long-term oral, previously chemically analyzed, Greek RJ administration to aged rats. Materials and methods RJ powder was given to 18-month old male Wistar rats (50 and 100 mg of powder/kg b.w./day) by gastric gavage for 2 months. The spatial memory was assessed in the water maze and next the level of neurotransmitters, their metabolites and utilization in the selected brain regions were estimated. Results The improvement of memory in rats pretreated with the smaller dose of RJ was observed compared with controls. In biochemical examination mainly the depletion of dopamine and serotonin in the prefrontal cortex along with an increase in their metabolite concentration and turnover were seen. Conclusion Better cognitive performance in the old animals using a non-toxic, natural food product in the view of the process of the aging of human population is noteworthy. Our results contribute towards validation of the traditional use of RJ in promoting a better quality of life in old age. © 2014 Elsevier Ireland Ltd. All rights reserved

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system. © 2018 Elsevier B.V

Administration of Greek Royal Jelly produces fast response in neurotransmission of aged Wistar male rats

Introduction. Royal Jelly (RJ) is a popular bee-derived product used widely in European and Asian traditional medicine. RJ has some pharmacological activities to support health and longevity as well as prevent ageing. Objectives. To evaluate whether a short-term 6-day Royal Jelly administration is able to induce behavioural and neurochemical effects in aged rats. Materials and method. RJ (previously chemically characterized by GC-FID and GC–MS) was given to 18-month-old male Wistar rats (100 and 500mg of powder/kg b.w./day) in subcutaneous injection for 6 days. Spatial memory was assessed in a water maze. Afterwards, the level of neurotransmitters, their metabolites and turnover in the selected brain regions were estimated by HPLC. Results. Short-term RJ administration did not change spatial memory in aged rats in the water maze, although it was sufficiently active to modify most of all the serotonergic and dopaminergic transmission in the prefrontal cortex and hippocampus. Conclusion. The obtained results indicate that Royal Jelly is able to affect very quickly the neurotransmission in the brain structures responsible for cognitive performance; however, short-term administration is not sufficient to exert behavioural consequences