Homage to Rita Levi-Montalcini. Molecular mechanisms of Alzheimer's disease: NGF modulation of APP processing

The therapeutic focus of the scientific community in Alzheimer's disease (AD) has been moving in the last years from attempting late rescue against cholinergic degeneration and amyloid beta plaque clearance to (i) the discovery of blood or cerebrospinal fluid markers for early diagnosis, and (ii) early therapeutic intervention with modulators of amyloid precursor protein (APP) processing. It is currently accepted idea that subtle synaptic alterations determine the first neuronal dysfunctions and cognitive deterioration, progressing overtime into neuronal degeneration in the sporadic and late onset form AD (LOAD), the most diffuse one (90% of AD cases). Synaptic loss occurs long before the appearance of a frank neuronal degeneration in LOAD. The perturbation of the nerve growth factor (NGF) signaling system in brain neurodegenerative disease like AD and Down's syndrome was for long time considered to be a pathological event, subsequent to amyloid-driven disruption of NGF retrograde transport from the cortex and hippocampus to the cell bodies of basal forebrain cholinergic neurons. Nowadays, an increasing amount of data indicate that the observed dysregulation of NGF-TrkA (tyrosine kinase A) and proNGF-p75NTR signaling systems is a good candidate for being the primus movens in the neuropathology of sporadic AD. Accordingly, an amyloid-independent strong correlation of cognitive deficits with reduction of NGF and TrkA, and accumulation of proNGF has been recently observed in mild cognitive impairment and its progression to AD. This review highlights the current knowledge about NGF and early events occurring in LOAD. The involvement of muscarinic acetylcholine receptors, cholesterol, sirtuin1, insulin-like growth factor-1, and Sunday driver protein in APP processing are also discussed. The studies reported here confirm a multitasking ability of NGF in slowing down, through both distinct and overlapping mechanisms, the amyloidogenic processing of APP in neurons of the central nervous system.Adipobiology 2013; 5: 7-18

Exploiting Focused Ultrasound to Aid Intranasal Drug Delivery for Brain Therapy

Novel effective therapeutic strategies are needed to treat brain neurodegenerative diseases and to improve the quality of life of patients affected by Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral sclerosis (ALS) as well as other brain conditions. At present no effective treatment options are available; current therapeutics for neurodegenerative diseases (NDs) improve cognitive symptoms only transiently and in a minor number of patients. Further, most of the amyloid-based phase III clinical trials recently failed in AD, in spite of promising preclinical and phase I-II clinical trials, further pinpointing the need for a better knowledge of the early mechanisms of disease as well as of more effective routes of drug administration. In fact, beyond common pathological events and molecular substrates, each of these diseases preferentially affect defined subpopulations of neurons in specific neuronal circuits (selective neuronal vulnerability), leading to the typical age-related clinical profile. In this perspective, key to successful drug discovery is a robust and reproducible biological validation of potential new molecular targets together with a concomitant set up of protocols/tools for efficient and targeted brain delivery to a specific area of interest. Here we propose and discuss Focused UltraSound aided drug administration as a specific and novel technical approach to achieve optimal concentration of the drug at the target area of interest. We will focus on drug delivery to the brain through the nasal route coupled to FUS as a promising approach to achieve neuroprotection and rescue of cognitive decline in several NDs

Violência contra mulher, um dado alarmante

A violência impacta cada dia mais o cotidiano das pessoas em geral, mas especificamente de mulheres que são vítimas de agressões. Sejam elas verbais, psicológicas, patrimoniais, físicas e/ou sexuais. Neste trabalho é realizada uma pesquisa descritiva sobre a violência e seus índices, com base nos dados da Polícia Civil do Estado do Rio Grande do Sul, Tribunal de Justiça do Rio Grande do Sul e no Atlas da Violência. Demonstrando os dados de violência contra a mulher no período de janeiro de 2020 a dezembro de 2022, em comparativo aos anos anteriores 2018 e 2019, englobando o período mais crítico da pandemia

The development of metal overlayers with smooth and rough topographies

A review of the recent advances made in the development of metal electrode surfaces with preferred crystallographic orientations and different roughnesses through the application of periodic potential treatments is presented. The different techniques are described for fcc metals in aqueous solutions with particular attention to platinum and gold. The probable mechanisms of the different electrochemical processes which are responsible for the changes in the surface structure of those metals are discussed. The possibility of modelling the growth of metal surface morphologies are considered as well as the importance of scanning tunneling microscopy imaging to assure the validity of proposed models.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta

Electrochemical faceting of single crystal platinum electrodes

The surface of a single crystal metallic sphere presents, in principle, all possible crystallographic planes. When such a surface structure is modified by one of the procedures described for the development of preferred orientation [ 1,2], one can develop a well defined atomic arrangement involving a certain particular crystallographic plane, depending on the set of parameters defining the fast potential perturbation. Due to the spherical geometry, the changes operating in the surface should require a very symmetrical stereospatial reconstruction, which results in the development of poles of the particular enhanced crystallographic plane and the disappearance of others.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta

Changes in the polycrystalline gold electrode surface produced by square wave potential perturbations

The electroreduction of gold oxide layers produced by a square wave potential signal (SWPS) under a proper set of perturbation conditions yields a reproducible electrode surface with a large increase in the surface area. The different variables are systematically investigated to establish the optimal conditions of the SWPS. The results are discussed on the basis of the thermodynamics and kinetics of oxide monolayer and multilayer formation.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA)Facultad de Ciencias Exacta

Desarrollo psicológico en niños de 2-5 años en poblaciones carenciadas : Los efectos de la institucionalización

Este trabajo se enmarca en la línea de evaluación del desarrollo psicológico y de sus determinantes. Está destinado a identificar los perfiles de desarrollo general y especifico que presentan los niños de 2/5 años de edad que provienen de sectores con necesidades básicas insatisfechas, cuya vida transcurre en diferentes contextos de crianza: la familia y la institución de guarda y la existencia o inexistencia de diferencias entre los indicadores del desarrollo general y el contexto de crianza. A partir de un diseño exploratorio descriptivo, teniendo en cuenta esos objetivos se seleccionaron de manera intencional dos grupos de participantes de ambos sexos, de 2/5 años de edad, sin patología neurológica ni retardo mental, procedentes de estrato social pobres, identificado por el nivel educacional y ocupacional de los padres.Eje: Psicología del desarrolloDepartamento de Psicologí

A novel effect. Changes in the electrochemical response of polycrystalline platinum promoted by very fast potential perturbations

It is well established that the voltammogram of polycrystalline platinum in acid electrolyte in the potential range corresponding to the stability of bulk water depends on the electrode history including the type of perturbation applied to the electrode and on the electrolyte composition.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta