The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model.

Mitochondrial dysfunctions critically impair nervous system development and are potentially involved in the pathogenesis of various neurodevelopmental disorders, including Down syndrome (DS), the most common genetic cause of intellectual disability. Previous studies from our group demonstrated impaired mitochondrial activity in peripheral cells from DS subjects and the efficacy of epigallocatechin-3-gallate (EGCG) - a natural polyphenol major component of green tea - to counteract the mitochondrial energy deficit. In this study, to gain insight into the possible role of mitochondria in DS intellectual disability, mitochondrial functions were analyzed in neural progenitor cells (NPCs) isolated from the hippocampus of Ts65Dn mice, a widely used model of DS which recapitulates many major brain structural and functional phenotypes of the syndrome, including impaired hippocampal neurogenesis. We found that, during NPC proliferation, mitochondrial bioenergetics and mitochondrial biogenic program were strongly compromised in Ts65Dn cells, but not associated with free radical accumulation. These data point to a central role of mitochondrial dysfunction as an inherent feature of DS and not as a consequence of cell oxidative stress. Further, we disclose that, besides EGCG, also the natural polyphenol resveratrol, which displays a neuroprotective action in various human diseases but never tested in DS, restores oxidative phosphorylation efficiency and mitochondrial biogenesis, and improves proliferation of NPCs. These effects were associated with the activation of PGC-1α/Sirt1/AMPK axis by both polyphenols. This research paves the way for using nutraceuticals as a potential therapeutic tool in preventing or managing some energy deficit-associated DS clinical manifestations

cAMP/PKA Signaling Modulates Mitochondrial Supercomplex Organization

The oxidative phosphorylation (OXPHOS) system couples the transfer of electrons to oxygen with pumping of protons across the inner mitochondrial membrane, ensuring the ATP production. Evidence suggests that respiratory chain complexes may also assemble into supramolecular structures, called supercomplexes (SCs). The SCs appear to increase the efficiency/capacity of OXPHOS and reduce the reactive oxygen species (ROS) production, especially that which is produced by complex I. Studies suggest a mutual regulation between complex I and SCs, while SCs organization is important for complex I assembly/stability, complex I is involved in the supercomplex formation. Complex I is a pacemaker of the OXPHOS system, and it has been shown that the PKA-dependent phosphorylation of some of its subunits increases the activity of the complex, reducing the ROS production. In this work, using in ex vivo and in vitro models, we show that the activation of cAMP/PKA cascade resulted in an increase in SCs formation associated with an enhanced capacity of electron flux and ATP production rate. This is also associated with the phosphorylation of the NDUFS4 subunit of complex I. This aspect highlights the key role of complex I in cellular energy production

Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases

In mammals, complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain has 31 supernumerary subunits in addition to the 14 conserved from prokaryotes to humans. Multiplicity of structural protein components, as well as of biogenesis factors, makes complex I a sensible pace-maker of mitochondrial respiration. The work reviewed here shows that the cAMP/PKA pathway regulates the biogenesis, assembly and catalytic activity of complex I and mitochondrial oxygen superoxide production. The structural, functional and regulatory complexity of complex I, renders it particularly vulnerable to genetic and sporadic pathological factors. Complex I dysfunction has, indeed, been found, to be associated with several human diseases. Knowledge of the pathogenetic mechanisms of these diseases can help to develop new therapeutic strategies. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions

Características agronômicas de cultivares de milho (Zea mays L.) e qualidade dos componentes e silagem

Este trabalho foi conduzido para se avaliarem as características agronômicas (acamamento, quebramento e produtividade) e químico-bromatólogicas da matéria verde e silagem de 19 cultivares de milho. Os tratamentos foram aplicados em parcelas de 5 x 4 m em um delineamento de blocos casualizados, com quatro repetições. Por ocasião da semeadura, aplicaram-se doses correspondentes a 500 kg/ha da fórmula 4-14-8 (N-P2O5-K2O) e, aos 47 dias da emergência, 60 kg/ha de N em cobertura. Entre as dezenove cultivares estudadas, selecionaram-se, com base na porcentagem de plantas quebradas e acamadas, nove com características agronômicas adequadas para colheita mecanizada. Ao atingirem o estádio grão farináceo, as plantas de milho da área útil (12 m²) foram colhidas e passadas em picadeira, para se obterem partículas de aproximadamente 2 cm. Depois de picada e homogeneizada, aproximadamente 15 kg de matéria verde foram colocados em sacos plásticos, eliminando o ar e, em seguida, transferidos para uma câmara escura, simulando assim as condições de um silo. A produção de matéria seca dos híbridos selecionados para serem ensilados não apresentou grandes variações, destacando-se o Zeneca 850 e o Braskalb XL380 com 12,72 e 12,62 t/ha de matéria seca, respectivamente. A porcentagem de espiga nas plantas e os teores de fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), carboidratos solúveis e digestibilidade in vitro da matéria seca dos híbridos não diferiram. Contudo, os teores de FDN, FDA, N-NH3/NT e DIVMS na silagem mostraram diferenças entre os nove híbridos, o que não se verificou para proteína bruta, ácido láctico e pH

Produção forrageira de gramíneas cultivadas sob luminosidade reduzida

O objetivo deste trabalho foi avaliar a influência de três níveis de sombreamento artificial (0,30 e 60%) sobre a produção de matéria seca, a concentração de nitrogênio e as características morfológicas de seis espécies de gramíneas forrageiras tropicais (Andropogon gayanus, cv. Planaltina, Brachiaria brizantha, cv. Marandu, B. decumbens, Melinis minutiflora, Panicum maximum, cv. Vencedor, e Setaria anceps, cv. Kazungula). Foi usado delineamento em blocos ao acaso, com parcelas subdivididas e quatro repetições; nas parcelas foram distribuídos os níveis de sombreamento e nas subparcelas, as espécies forrageiras. Os resultados demonstram que o sombreamento influenciou a produção de matéria seca, a concentração de N e as características morfológicas das espécies avaliadas. A produção forrageira foi influenciada diferencialmente pelo sombreamento. A produção de matéria seca do P. maximum, cv. Vencedor foi 19,72% maior à sombra moderada que a pleno sol. A produção de S. anceps, cv. Kazungula, entretanto, não foi influenciada pelo sombreamento. As demais espécies tiveram decréscimo da produção de matéria seca com a redução da luminosidade. Em todas as espécies, houve aumento da concentração de N e redução do teor de matéria seca da forragem, que se tornou mais suculenta à sombra. As características morfológicas não apresentaram comportamento padrão, variando conforme a espécie avaliada.The objective of this work was to evaluate the influence of three levels of artificial shade (0, 30 and 60%) on dry matter production, nitrogen content and morphological characteristics of six forage grasses (Andropogon gayanus cv. Planaltina, Brachiaria brizantha cv. Marandu, B. decumbens, Melinis minutiflora, Panicum maximum cv. Vencedor and Setaria anceps cv. Kazungula). A randomized block design, with split plots and four replicates, was used; the shading levels were allotted to the plots and the species to the split plots. The results showed that shading affected the production of dry matter, the nitrogen content and the morphological characteristics of the evaluated species. The production of forage was differentially affected by the shade. The dry matter production of P. maximum cv. Vencedor was 19.72% higher, at moderate shade than in broad daylight. The forage production of S. anceps cv. Kazungula, however, was not affected by the shade. The dry matter production of other species decreased with the reduction of the light. In all species there was an increase of N content and reduction of the content of dry matter of the forage, which became juicier in the shade. The morphological characteristics did not show a standard behavior, which varied according to the studied specie