Potencialidades e fragilidades no processo de compra e venda de produtos orgânicos da agricultura familiar para a alimentação escolar em municípios da região sul do Brasil

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Nutrição, Florianópolis, 2018.O Programa Nacional de Alimentação Escolar, ao inserir alimentos orgânicos da agricultura familiar no mercado das políticas públicas, contribui para a redução da pobreza e da insegurança alimentar no campo e incentiva a organização das propriedades rurais. Além disso, oferece alimentos de qualidade aos escolares. Dessa forma, estimula a produção desses alimentos, gerando muitos benefícios às questões ambientais, sociais e de saúde pública. O objetivo do estudo foi avaliar as potencialidades e fragilidades no processo de compra e venda de produtos orgânicos da agricultura familiar para a alimentação escolar, em municípios da região Sul do Brasil, no ano de 2015, por meio de entrevistas realizadas com informantes-chave da alimentação escolar. Foram estudados 21 municípios e entrevistados 111 informantes; dentre eles, nutricionistas, agricultores, engenheiros agrônomos, técnicos agrícolas, representantes de cooperativas/sindicatos, secretários de agricultura e extensionistas rurais. Os dados quantitativos foram transferidos para uma planilha do Microsoft Excel e as análises foram realizadas no programa Stata (Stata Corporation College Station, EUA), versão 11.0, por meio do teste Exato de Fisher. As variáveis foram inicialmente analisadas descritivamente com base na distribuição de frequência (absoluta e relativa). As variáveis de dificuldades relacionadas à oferta de produtos orgânicos foram estratificadas por estado e, posteriormente, agrupadas por entrevistado. Os dados qualitativos foram transcritos em verbatim e importados para o software (Nvivo) para realização de Análise de Conteúdo (BARDIN, 2004). A maioria dos municípios (90,5%) não comprou alimentos orgânicos da agricultura familiar em 2015. A pouca disponibilidade de mercado fornecedor e a baixa produção de alimentos orgânicos foram as dificuldades mais apontadas para o processo da compra e para o processo da venda de alimentos orgânicos para alimentação escolar. Os entrevistados reconheceram que a divulgação dos benefícios dos alimentos orgânicos se a busca por informações e a certificação participativa contribuíram para superar as dificuldades de produção de orgânicos nos municípios. Considera-se que a valorização dos alimentos orgânicos é o ponto-chave para o aumento da oferta e incentivo ao agricultor na produção.Abstract : The National School Feeding Program introducing organic food from family farms into the public policy market contributes to reducing poverty and food insecurity in the countryside and encourages rural properties organization. In addition, it offers quality food to schoolchildren. In this way it stimulates the production of these foods, providing many benefits to environmental, social and public health issues. The objective of the study was to evaluate the potentialities and weakness in the process of buying and selling organic products from family agriculture to school feeding in municipalities of the southern region of Brazil, in 2015 through interviews with key informants in school feeding. A total of 21 municipalities were interviewed and 111 informants, among them nutritionists, farmers, agronomists, agricultural technicians, representatives of cooperative /syndicates, agricultural secretaries and rural extension workers were interviewed. Quantitative datas were transferred to a Microsoft Excel spreadsheet and analyzes were performed using Stata Corporation (Stata Corporation College Station, USA) version 11.0 using the Fisher Exact test. The variables were initially analyzed descriptively based on the frequency distribution (absolute and relative). The variables of difficulties related to the supply of organic products were stratified by state and later grouped bythe interviewee. The qualitative datas were transcribed in verbatim and imported into the software (Nvivo) to perform Content Analysis (Bardin, 2004). The majority of municipalities (90.5%) did not purchase organic food from family farms in 2015. The low availability of the supplier market and the low production of organic foods were the difficulties most pointed in the process of buying and selling organic food school. The interviewees acknowledged that the disclosure of the organic food benefits, as well as the search for information and participatory certification, have contributed to overcome the difficulties of organic production in the municipalities. It is considered that the organic food appreciation is the key point to increase food demand, providing the increase of the offer and consequently incentives to the farmer`s production

Mild inflammatory profile without gliosis in the c-rel deficient mouse modeling a late-onset parkinsonism

The impact of neuroinflammation and microglial activation to Parkinson’s disease (PD) progression is still debated. Post-mortem analysis of PD brains has shown that neuroinflammation and microgliosis are key features of end-stage disease. However, microglia neuroimaging studies and evaluation of cerebrospinal fluid (CSF) cytokines in PD patients at earlier stages do not support the occurrence of a pronounced neuroinflammatory process. PD animal models recapitulating the motor and non-motor features of the disease, and the slow and progressive neuropathology, can be of great advantage in understanding whether and how neuroinflammation associates with the onset of symptoms and neuronal loss. We recently described that 18-month-old NF-κB/c-Rel deficient mice (c-rel−/−) develop a spontaneous late-onset PD-like phenotype encompassing L-DOPA-responsive motor impairment, nigrostriatal neuron degeneration, α-synuclein and iron accumulation. To assess whether inflammation and microglial activation accompany the onset and the progression of PD-like pathology, we investigated the expression of cytokines (interleukin 1 beta (Il1b), interleukin 6 (Il6)) and microglial/macrophage activation markers (Fc gamma receptor III (Fcgr3), mannose receptor 1 (Mrc1), chitinase-like 3 (Ym1), arginase 1 (Arg 1), triggering receptor expressed on myeloid cells 2 (Trem2)), together with microglial ionized calcium binding adapter molecule 1 (Iba1) and astrocyte glial fibrillary acidic protein (GFAP) immunolabeling, in the substantia nigra (SN) of c-rel−/− mice, at premotor (4- and 13-month-old) and motor phases (18-month-old). By quantitative real-time RT-PCR we found increased M2c microglial/macrophage markers expression (Mrc1 and Arg1) in 4-month-old c-rel−/− mice. M2-type transcription dropped down in 13-month-old c-rel−/− mice. At this age, the pro-inflammatory Il1b, but not Il6 or the microglia-macrophage M1-polarization marker Fcgr3/CD16, increased when compared to wild-type (wt). Furthermore, no significant variation in the transcription of inflammatory and microglial/macrophage activation genes was present in 18-month-old c-rel−/− mice, that display motor dysfunctions and dopaminergic neuronal loss. Immunofluorescence analysis of Iba1-positive cells in the SN revealed no sign of overt microglial activation in c-rel−/− mice at all the time-points. MRC1-Iba1-positive cells were identified as non-parenchymal macrophages in 4-month-old c-rel−/− mice. Finally, no sign of astrogliosis was detected in the SN of the diverse animal groups. In conclusion, this study supports the presence of a mild inflammatory profile without evident signs of gliosis in c-rel−/− mice up to 18 months of age. It suggests that symptomatic PD-like phenotype can develop in the absence of concomitant severe inflammatory process

Signal transduction and epigenetic mechanisms in the control of microglia activation during neuroinflammation

Activation of microglia is a common denominator and a pathophysiological hallmark of the central nervous system (CNS) disorders. Damage or CNS disorders can trigger inflammatory responses in resident microglia and initiate a systemic immune system response. Although a repertoire of inflammatory responses differs in those diseases, there is a spectrum of transcriptionally activated genes that encode various mediators such as growth factors, inflammatory cytokines, chemokines, matrix metalloproteinases, enzymes producing lipid mediators, toxic molocules, all of which contribute to neuroinflammation. The initiation, progression and termination of inflammation requires global activation of gene expression, postranscriptional regulation, epigenetic modifications, changes in chromatin structure and these processes are tightly regulated by specific signaling pathways. This review focuses on the function of "master regulators" and epigenetic mechanisms in microglia activation during neuroinflammation. We review studies showing impact of epigenetic enzyme inhibitors on microglia activation in vitro and in vivo, and critically discuss potential of such molecules to prevent/moderate pathological events mediated by microglia under brain pathologies.(1)

The End Is the Beginning: Parkinson's Disease in the Light of Brain Imaging

Parkinson's disease (PD), the most common neurodegenerative disorder, is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healin

Opposing Roles for NF-κB/Rel Factors p65 and c-Rel in the Modulation of Neuron Survival Elicited by Glutamate and Interleukin-1β

The nuclear transcription factors NF-kappaB/Rel have been shown to function as key regulators of either cell death or survival in neuronal cells. Here, we investigated whether selective activation of diverse NF-kappaB/Rel family members might lead to distinct effects on neuron viability. In both cultured rat cerebellar granule cells and mouse hippocampal slices, we examined NF-kappaB/Rel activation induced by two opposing modulators of cell viability: 1) interleukin-1beta (IL-1beta), which promotes neuron survival and 2) glutamate, which can elicit toxicity. IL-1beta produced a prolonged stimulation of NF-kappaB/Rel factors by inducing both IkappaBalpha and IkappaBbeta degradation. Glutamate produced a delayed and transient activation of NF-kappaB/Rel, which was associated with a brief loss of IkappaBalpha. Moreover, IL-1beta activated the p50, p65, and c-Rel subunits of NF-kappaB/Rel, whereas glutamate activated only the p50 and p65 proteins. The inhibition of NF-kappaB/Rel protein expression by antisense oligonucleotides in cerebellar granule cells showed that p65 was involved in glutamate-mediated cell death, whereas c-Rel was essential for IL-1beta-preserved cell survival. Furthermore, the depletion of c-Rel in cultured neurons as well as in the hippocampus from the c-Rel(-/-) mouse converted the IL-1beta effect into toxicity. These findings suggest that, within a single neuron, the balance between cell death and survival in response to external stimuli may rely on the activation of distinct NF-kappaB/Rel proteins

Age-dependent neuropsychiatric symptoms in the NF-κB/c-Rel knockout mouse model of Parkinson's Disease

Non-motor symptoms are frequently observed in Parkinson's disease (PD) and precede the onset of motor deficits by years. Among them, neuropsychiatric symptoms, including anxiety, depression, and apathy, are increasingly considered as a major challenge for patients with PD and their caregivers. We recently reported that mice lacking the nuclear factor-κB (NF-κB)/c-Rel protein (c-rel-/- mice) develop an age-dependent PD-like pathology and phenotype characterized by the onset of non-motor symptoms, including constipation and hyposmia, starting at 2 months of age, and motor deficits at 18 months. To assess whether c-rel-/- mice also suffer from neuropsychiatric symptoms, in this study we tested different cohorts of wild-type (wt) and c-rel-/- mice at 3, 6, 12, and 18-20 months with different behavioral tests. Mice lacking c-Rel displayed anxiety and depressive-like behavior starting in the premotor phase at 12 months, as indicated by the analysis with the open field (OF) test and the forced swim test with water wheel (FST), respectively. A deficit in the goal-oriented nesting building test was detected at 18-20 months, suggesting apathetic behavior. Taken together, these results indicate that c-rel-/- mice recapitulate the onset and the progression of PD-related neuropsychiatric symptoms. Therefore, this animal model may represent a valuable tool to study the prodromal stage of PD and for testing new therapeutic strategies to alleviate neuropsychiatric symptoms

NF-κB in Innate Neuroprotection and Age-Related Neurodegenerative Diseases

NF-κB factors are cardinal transcriptional regulators of inflammation and apoptosis, involved in the brain programing of systemic aging and in brain damage. The composition of NF-κB active dimers and epigenetic mechanisms modulating histone acetylation, finely condition neuronal resilience to brain insults. In stroke models, the activation of NF-κB/c-Rel promotes neuroprotective effects by transcription of specific anti-apoptotic genes. Conversely, aberrant activation of NF-κB/RelA showing reduced level of total acetylation, but site-specific acetylation on lysine 310, triggers the expression of pro-apoptotic genes. Constitutive knockout of c-Rel shatters the resilience of substantia nigra (SN) dopaminergic (DA) neurons to aging and induces a parkinsonian like pathology in mice. c-rel(-/-) mice show increased level of aberrantly acetylated RelA in the basal ganglia, neuroinflammation, accumulation of alpha-synuclein, and iron. Moreover, they develop motor deficits responsive to l-DOPA treatment and associated with loss of DA neurons in the SN. Here, we discuss the effect of unbalanced activation of RelA and c-Rel during aging and propose novel challenges for the development of therapeutic strategies in neurodegenerative diseases

A Polyphenol-Enriched Supplement Exerts Potent Epigenetic-Protective Activity in a Cell-Based Model of Brain Ischemia

Bioactive components, due in part to their epigenetic properties, are beneficial for preventing several human diseases including cerebrovascular pathologies. However, no clear demonstration supports the idea that these molecules still conserve their epigenetic effects when acting at very low concentrations reproducing the brain levels achieved after oral administration of a micronutrient supplement. In the present study, we used a cellular model of brain ischemia to investigate the neuroprotective and epigenetic activities of a commercially available micronutrient mixture (polyphenol-enriched micronutrient mixture, PMM) enriched in polyphenols ((-)-epigallocatechin-3-gallate, quercetin, resveratrol), α-lipoic acid, vitamins, amino acids and other micronutrients. Mimicking the suggested dietary supplementation, primary cultures of mouse cortical neurons were pre-treated with PMM and then subjected to oxygen glucose deprivation (OGD). Pre-treatment with PMM amounts to provide bioactive components in the medium in the nanomolar range potently prevented neuronal cell death. The protection was associated with the deacetylation of the lysin 310 (K310) on NF-κB/RelA as well as the deacetylation of H3 histones at the promoter of Bim, a pro-apoptotic target of ac-RelA(K310) in brain ischemia. Epigenetic regulators known to shape the acetylation state of ac-RelA(K310) moiety are the histone acetyl transferase CBP/p300 and the class III histone deacetylase sirtuin-1. In view of that evidence, the protection we here report unveils the efficacy of bioactive components endowed with either inhibitory activity on CBP/p300 or stimulating activity on the AMP-activated protein kinase⁻sirtuin 1 pathway. Our results support a potential synergistic effect of micronutrients in the PMM, suggesting that the intake of a polyphenol-based micronutrient mixture can reduce neuronal vulnerability to stressful conditions at concentrations compatible with the predicted brain levels reached by a single constituent after an oral dose of PMM

The Contribution of -Synuclein Spreading to Parkinson’s Disease Synaptopathy

Synaptopathies are diseases with synapse defects as shared pathogenic features, encompassing neurodegenerative disorders such as Parkinson’s disease (PD). In sporadic PD, the most common age-related neurodegenerative movement disorder, nigrostriatal dopaminergic deficits are responsible for the onset of motor symptoms that have been related to -synuclein deposition at synaptic sites. Indeed, -synuclein accumulation can impair synaptic dopamine release and induces the death of nigrostriatal neurons. While in physiological conditions the protein can interact with and modulate synaptic vesicle proteins and membranes, numerous experimental evidences have confirmed that its pathological aggregation can compromise correct neuronal functioning. In addition, recent findings indicate that -synuclein pathology spreads into the brain and can affect the peripheral autonomic and somatic nervous system. Indeed, monomeric, oligomeric, and fibrillary -synuclein can move from cell to cell and can trigger the aggregation of the endogenous protein in recipient neurons. This novel “prion-like” behavior could further contribute to synaptic failure in PD and other synucleinopathies. This review describes the major findings supporting the occurrence of -synuclein pathology propagation in PD and discusses how this phenomenon could induce or contribute to synaptic injury and degeneration