What We Know about Euterpe Genus and Neuroprotection: A Scoping Review.

The Euterpe genus (mainly Euterpe oleracea Martius, Euterpe precatoria Martius, and Euterpe edulis Martius) has recently gained commercial and scientific notoriety due to the high nutritional value of its fruits, which are rich in polyphenols (phenolic acids and anthocyanins) and have potent antioxidant activity. These characteristics have contributed to the increased number of neuropharmacological evaluations of the three species over the last 10 years, especially açaí of the species Euterpe oleracea Martius. The fruits of the three species exert neuroprotective effects through the modulation of inflammatory and oxidative pathways and other mechanisms, including the inhibition of the mTOR pathway and protection of the blood-brain barrier, all of them intimately involved in several neuropathologies. Thus, a better understanding of the neuropharmacological properties of these three species may open new paths for the development of therapeutic tools aimed at preventing and treating a variety of neurological conditions.

Polymorphisms in immune-mediator genes and the risk of dengue virus infection: Lights from a systematic revaluation by Bayesian approaches.

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.

Microglial Metamorphosis in Three Dimensions in Virus Limbic Encephalitis: An Unbiased Pictorial Representation Based on a Stereological Sampling Approach of Surveillant and Reactive Microglia.

Microglia influence pathological progression in neurological diseases, reacting to insults by expressing multiple morphofunctional phenotypes. However, the complete morphological spectrum of reactive microglia, as revealed by three-dimensional microscopic reconstruction, has not been detailed in virus limbic encephalitis. Here, using an anatomical series of brain sections, we expanded on an earlier Piry arbovirus encephalitis study to include CA1/CA2 and assessed the morphological response of homeostatic and reactive microglia at eight days post-infection. Hierarchical cluster and linear discriminant function analyses of multimodal morphometric features distinguished microglial morphology between infected animals and controls. For a broad representation of the spectrum of microglial morphology in each defined cluster, we chose representative cells of homeostatic and reactive microglia, using the sum of the distances of each cell in relation to all the others. Based on multivariate analysis, reactive microglia of infected animals showed more complex trees and thicker branches, covering a larger volume of tissue than in control animals. This approach offers a reliable representation of microglia dispersion in the Euclidean space, revealing the morphological kaleidoscope of surveillant and reactive microglia morphotypes. Because form precedes function in nature, our findings offer a starting point for research using integrative methods to understand microglia form and function.

Microglial Morphology Across Distantly Related Species: Phylogenetic, Environmental and Age Influences on Microglia Reactivity and Surveillance States.

Microglial immunosurveillance of the brain parenchyma to detect local perturbations in homeostasis, in all species, results in the adoption of a spectrum of morphological changes that reflect functional adaptations. Here, we review the contribution of these changes in microglia morphology in distantly related species, in homeostatic and non-homeostatic conditions, with three principal goals (1): to review the phylogenetic influences on the morphological diversity of microglia during homeostasis (2); to explore the impact of homeostatic perturbations (Dengue virus challenge) in distantly related species (Mus musculus and Callithrix penicillata) as a proxy for the differential immune response in small and large brains; and (3) to examine the influences of environmental enrichment and aging on the plasticity of the microglial morphological response following an immunological challenge (neurotropic arbovirus infection). Our findings reveal that the differences in microglia morphology across distantly related species under homeostatic condition cannot be attributed to the phylogenetic origin of the species. However, large and small brains, under similar non-homeostatic conditions, display differential microglial morphological responses, and we argue that age and environment interact to affect the microglia morphology after an immunological challenge; in particular, mice living in an enriched environment exhibit a more efficient immune response to the virus resulting in earlier removal of the virus and earlier return to the homeostatic morphological phenotype of microglia than it is observed in sedentary mice.

Influence of enriched environment on viral encephalitis outcomes: behavioral and neuropathological changes in albino Swiss mice.

An enriched environment has previously been described as enhancing natural killer cell activity of recognizing and killing virally infected cells. However, the effects of environmental enrichment on behavioral changes in relation to virus clearance and the neuropathology of encephalitis have not been studied in detail. We tested the hypothesis that environmental enrichment leads to less CNS neuroinvasion and/or more rapid viral clearance in association with T cells without neuronal damage. Stereology-based estimates of activated microglia perineuronal nets and neurons in CA3 were correlated with behavioral changes in the Piry rhabdovirus model of encephalitis in the albino Swiss mouse. Two-month-old female mice maintained in impoverished (IE) or enriched environments (EE) for 3 months were behaviorally tested. After the tests, an equal volume of Piry virus (IEPy, EEPy)-infected or normal brain homogenates were nasally instilled. Eight days post-instillation (dpi), when behavioral changes became apparent, brains were fixed and processed to detect viral antigens, activated microglia, perineuronal nets, and T lymphocytes by immuno- or histochemical reactions. At 20 or 40 dpi, the remaining animals were behaviorally tested and processed for the same markers. In IEPy mice, burrowing activity decreased and recovered earlier (8-10 dpi) than open field (20-40 dpi) but remained unaltered in the EEPy group. EEPy mice presented higher T-cell infiltration, less CNS cell infection by the virus and/or faster virus clearance, less microgliosis, and less damage to the extracellular matrix than IEPy. In both EEPy and IEPy animals, CA3 neuronal number remained unaltered. The results suggest that an enriched environment promotes a more effective immune response to clear CNS virus and not at the cost of CNS damage.

Hippocampus and dentate gyrus of the Cebus monkey: architectonic and stereological study.

Behavioral, electrophysiological, and anatomical assays of non-human primates have provided substantial evidence that the hippocampus and dentate gyrus are essential for memory consolidation. However, a single anatomical and stereological investigation of these regions has been done in New World primates to complement those assays. The aim of the present study was to describe the cyto-, myelo-, and histochemical architecture of the hippocampus and dentate gyrus, and to use the optical fractionator method to estimate the number of neurons in the hippocampal pyramidal and granular neurons in the dentate gyrus of the Cebus monkey. NeuN immunolabeling, lectin histochemical staining with Wisteria floribunda agglutinin (WFA), enzyme-histochemical detection of NADPH-diaphorase activity and Gallyas silver staining were used to define the layers and limits of the hippocampal fields and dentate gyrus. A comparative analysis of capuchin (Cebus apella) and Rhesus (Macaca mulatta) monkeys revealed similar structural organization of these regions but significant differences in the regional distribution of neurons. C. apella were found to have 1.3 times fewer pyramidal and 3.5 times fewer granular neurons than M. mulatta. Taken together the architectonic and stereological data of the present study suggest that hippocampal and dentate gyrus neural networks in the C. apella and M. mulatta may contribute to hippocampal-dentate gyrus-dependent tasks in different proportions.