Balance actuación SIPHO 2020

Sol·licitant de l’informe: Institut Municipal de l'Habitatge i Rehabilitació (Barcelona)Les mencions de responsabilitat s'han basat en els crèdits facilitats per l'àrea responsabl

The role of leptin in the sporadic form of Alzheimer's disease. Interactions with the adipokines amylin, ghrelin and the pituitary hormone prolactin

Leptin (Lep) is emerging as a pivotal molecule involved in both the early events and the terminal phases of Alzheimer's disease (AD). In the canonical pathway, Lep acts as an anorexigenic factor via its effects on hypothalamic nucleus. However, additional functions of Lep in the hippocampus and cortex have been unravelled in recent years. Early events in the sporadic form of AD likely involve cellular level alterations which can have an effect on food intake and metabolism. Thus, AD can be conceivably interpreted as a multiorgan pathology that not only results in a dramatic neuronal loss in brain areas such as the hippocampus and the cortex (ultimately leading to a significant cognitive impairment) but as a disease which also affects body-weight homeostasis. According to this view, body-weight control disruptions are to be expected in both the early- and late-stage AD, concomitant with changes in serum Lep content, alterations in Lep transport across the blood-brain barrier (BBB) and Lep receptor-related signalling abnormalities. Lep is a member of the adipokine family of molecules, while the Lep receptor belongs to the class I cytokine receptors. Since cellular response to adipokine signalling can be either potentiated or diminished as a result of specific ligand-receptor interactions, Lep interactions with other members of the adipokine family including amylin, ghrelin and hormones such as prolactin require further investigation. In this review, we provide a general perspective on the functions of Lep in the brain, with a particular focus on the sporadic AD. © 2015 Elsevier Inc

Neuroprotective and anti-ageing role of leptin

Leptin (Lep), an adipose-derived hormone, exerts very important functions in the body mainly on energy storage and availability. The physiological effects of Lep controlling the body weight and suppressing appetite are mediated by the long form of Lep receptor in the hypothalamus. Lep receptor activates several downstream molecules involved in key pathways related to cell survival such as STAT3, PI3K, MAPK, AMPK, CDK5 and GSK3b. Collectively, these pathways act in a coordinated manner and form a network that is fully involved in Lep physiological response. Although the major interest in Lep is related to its role in the regulation of energy balance, and since resistance to Lep affects is the primary risk factor for obesity, the interest on their effects on brain cognition and neuroprotection is increasing. Thus, Lep and Lep mimetic compounds now await and deserve systematic exploration as the orchestrator of protective responses in the nervous system. Moreover, Lep might promote the activation of a cognitive process that may retard or even partially reverse selected aspects of Alzheimer's disease or ageing memory loss. © 2012 Society for Endocrinology

Molecular links between early energy metabolism alterations and Alzheimer´s disease

Recent studies suggest that the neurobiology of Alzheimer's disease (AD) pathology could not be explained solely by an increase in beta-amyloid levels. In fact, success with potential therapeutic drugs that inhibit the generation of beta amyloid has been low. Therefore, due to therapeutic failure in recent years, the scientists are looking for alternative hypotheses to explain the causes of the disease and the cognitive loss. Accordingly, alternative hypothesis propose a link between AD and peripheral metabolic alteration. Then, we review in depth changes related to insulin signalling and energy metabolism in the context of the APPSwe/PS1dE9 (APP/PS1) mice model of AD. We show an integrated view of the changes that occur in the early stages of the amyloidogenic process in the APP/PS1 double transgenic mice model. These early changes affect several key metabolic processes related to glucose uptake and insulin signalling, cellular energy homeostasis, mitochondrial biogenesis and increased Tau phosphorylation by kinase molecules like mTOR and Cdk5

Melatonin suppresses nitric oxide production in glial cultures by proinflammatory cytokines through p38 MAPK inhibition.

10.3109/10715762.2013.845295Melatonin has been shown to down-regulate inflammatory responses and provide neuroprotection. However, the mechanisms underlying the anti-inflammatory properties of melatonin are poorly understood. In the present work, we studied the modulatory effect of melatonin against pro-inflammatory cytokines in glial cell cultures. Treatment with pro-inflammatory cytokines mainly tumor necrosis factor-alpha, interleukin 1-beta, and interferon-gamma induces an increase in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. Pre-treatment with melatonin produced an inhibitory effect on iNOS expression and NO production. The biochemical studies revealed that cytokine treatment favors the activation of several pathways, such as mitogen-activated protein kinases (MAPKs), STAT1, and STAT3; however, the anti-inflammatory effect of melatonin was accompanied only by a decrease in p38 MAPK activity. Likewise, SB203580 a p38 kinase inhibitor inhibits NO production. These data indicate that the anti-inflammatory action of melatonin in glial cells after stimulation with pro-inflammatory cytokines may be in part, attributable to p38 inhibition which down-regulates iNOS expression and NO production

Molecular links between early energy metabolism alterations and Alzheimer´s disease

Recent studies suggest that the neurobiology of Alzheimer's disease (AD) pathology could not be explained solely by an increase in beta-amyloid levels. In fact, success with potential therapeutic drugs that inhibit the generation of beta amyloid has been low. Therefore, due to therapeutic failure in recent years, the scientists are looking for alternative hypotheses to explain the causes of the disease and the cognitive loss. Accordingly, alternative hypothesis propose a link between AD and peripheral metabolic alteration. Then, we review in depth changes related to insulin signalling and energy metabolism in the context of the APPSwe/PS1dE9 (APP/PS1) mice model of AD. We show an integrated view of the changes that occur in the early stages of the amyloidogenic process in the APP/PS1 double transgenic mice model. These early changes affect several key metabolic processes related to glucose uptake and insulin signalling, cellular energy homeostasis, mitochondrial biogenesis and increased Tau phosphorylation by kinase molecules like mTOR and Cdk5

Neotropical ornithology: Reckoning with historical assumptions, removing systemic barriers, and reimagining the future

A major barrier to advancing ornithology is the systemic exclusion of professionals from the Global South. A recent special feature, Advances in Neotropical Ornithology, and a shortfalls analysis therein, unintentionally followed a long-standing pattern of highlighting individuals, knowledge, and views from the Global North, while largely omitting the perspectives of people based within the Neotropics. Here, we review current strengths and opportunities in the practice of Neotropical ornithology. Further, we discuss problems with assessing the state of Neotropical ornithology through a northern lens, including discovery narratives, incomplete (and biased) understanding of history and advances, and the promotion of agendas that, while currently popular in the north, may not fit the needs and realities of Neotropical research. We argue that future advances in Neotropical ornithology will critically depend on identifying and addressing the systemic barriers that hold back ornithologists who live and work in the Neotropics: unreliable and limited funding, exclusion from international research leadership, restricted dissemination of knowledge (e.g., through language hegemony and citation bias), and logistical barriers. Moving forward, we must examine and acknowledge the colonial roots of our discipline, and explicitly promote anti-colonial agendas for research, training, and conservation. We invite our colleagues within and beyond the Neotropics to join us in creating new models of governance that establish research priorities with vigorous participation of ornithologists and communities within the Neotropical region. To include a diversity of perspectives, we must systemically address discrimination and bias rooted in the socioeconomic class system, anti-Blackness, anti-Brownness, anti-Indigeneity, misogyny, homophobia, tokenism, and ableism. Instead of seeking individual excellence and rewarding top-down leadership, institutions in the North and South can promote collective leadership. In adopting these approaches, we, ornithologists, will join a community of researchers across academia building new paradigms that can reconcile our relationships and transform science. Spanish and Portuguese translations are available in the Supplementary Material.• Research conducted by ornithologists living and working in Latin America and the Caribbean has been historically and systemically excluded from global scientific paradigms, ultimately holding back ornithology as a discipline.• To avoid replicating systems of exclusion in ornithology, authors, editors, reviewers, journals, scientific societies, and research institutions need to interrupt long-held assumptions, improve research practices, and change policies around funding and publication.• To advance Neotropical ornithology and conserve birds across the Americas, institutions should invest directly in basic field biology research, reward collective leadership, and strengthen funding and professional development opportunities for people affected by current research policies.Peer reviewe