Age-dependent multisystem parkinsonian features in a novel neuromelanin-producing transgenic mouse model

Trabajo presentado en el 19th National Meeting of the Spanish Society of Neuroscience, celebrado en Lleida (España), del 3 al 5 de noviembre de 2021Parkinson’s disease (PD) is characterized by a preferential degeneration of neurons that accumulate with age the pigment neuromelanin, especially neurons from substantia nigra (SN) and locus coeruleus (LC). We aim to characterize the consequences of age-dependent intracellular neuromelanin accumulation in catecholaminergic neuronal populations to understand the relationship between this process and the vulnerability of these cells in PD, as well as its impact on healthy brain aging. We previously generated a rat model exhibiting progressive unilateral SN production of neuromelanin that showed parkinsonian-like neuropathology and motor deficits1. Here, we generated a new neuromelanin-producing rodent model, based on the tissue-specific constitutive expression of human tyrosinase (hTyr) under the tyrosine hydroxylase (TH) promoter (Tg-TH-hTyr), that mimics the bilateral distribution of pigmentation within the aging human brain (i.e. catecholaminergic groups A1-A142). In parallel to neuromelanin intracellular buildup, Tg-TH-hTyr mice exhibited major PD features, including motor and non-motor behavioral alterations, inclusion body formation and degeneration of specific catecholaminergic neuronal groups. Genome-wide transcriptomic analysis of neuromelanin-laden neurons revealed alterations in PD-related biological pathways that correlate with human PD postmortem studies. Our results show that modelling human neuromelanin accumulation in rodents leads to age-dependent catecholaminergic dysfunction and molecular alterations resulting in motor and non-motor deficits, which is relevant to PD pathology and brain aging.Peer reviewe

Shaping public Opinion for confrontation : catalan independence claims as represented in spanish, catalan, valencian, and basque editorials

Editorials represent a newspaper's principal means of ideological positioning and serve to identify the attitude of each newspaper and its readership to some of the main actors in any given conflict, especially those that are political in nature. Catalonia's independence movement has experienced a surge in recent years. The turning point came in July 2010, after Spain's constitutional court ruled against some aspects of Catalonia's Statute of Autonomy (the legislation regulating the relationship between the Catalan autonomous community and the Spanish state). The ruling annulled some of the articles of the statute. The demonstration in support of Catalan independence that took place on September 11, 2012, was considered the most important among several mass rallies held for this purpose over successive years on Catalonia's National Day. This article presents the results of a qualitative and quantitative analysis of editorial articles published around these two key dates, with the goal of studying each newspaper's treatment of political actors and their degree of identification with these actors. Their use of arguments aimed at persuading readers and legitimizing a given position during the specified time periods in 2010 and 2012 will also be studied. The study focuses on the editorial articles published by several newspapers in four distinct regional contexts: Catalonia, Valencia, the Basque Country, as well as the whole of Spain. The analyzed articles were published a few days before and after July 10, 2010, and September 11, 2012

Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts

Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis

Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, H2O2, hypoxia, glucose-deprivation and glutamate excitotoxicity yielded − 58, − 61, − 29, − 45 and − 49% injury, respectively, with a dose-response relationship found only for H2O2 injury (R2 = 29.29%, p I2 = 99.36%, df = 132, p R2 = 44.77%, p R2 = 28.64%, p R2 = 4.13%, p p 2O2 injury reported only improvement. In studies using glucose deprivation, intervention generally worsened outcome. There was insufficient data to rank individual interventions, but of the studies reporting greatest improvement (> 90% effect size), 7/13 were of herbal medicine constituents (24.85% of the intervention dataset). We conclude that surprisingly little is known of the human neuronal response to ischaemic injury, and that the large impact of methodology on outcome indicates that further model validation is required. Lack of evidence for randomisation, blinding or power analysis suggests that the intervention data is at substantial risk of bias

Towards a molecular understanding of the role of lipids in Parkinson’s disease

Contains fulltext : 218638.pdf (publisher's version ) (Open Access)Radboud University, 20 mei 2020Promotores : Wieringa, B., Martens, G.J.M

Explorative Combined Lipid and Transcriptomic Profiling of Substantia Nigra and Putamen in Parkinson's Disease

Contains fulltext : 225767.pdf (publisher's version ) (Open Access)22 p