Sonia Martínez-Páramo’s research while affiliated with University of Valladolid and other places

Adult brain neural precursors carry out their biological activity in specific areas in which they are able to self-renew and differentiate into neurons. This is due to a complex microenvironment of cellular interrelations in which soluble factors from the neighboring cells, vascular structures, and the content of the brain ventricle cavity (cerebrospinal fluid) play a key role. This cellular functional entity, known as the “neurogenic niche,” is able to generate new mature neurons, which are functionally integrated into the neuronal circuits of the adult mammal brain. The complexity of neurogenic niche signaling, which include biologically active molecules such as growth factors and morphogens, requires an experimental approach in order to create specific modifications of the biological activity of some of these molecules by means of a model of the active neurogenic niche, allowing an evaluation of neural precursor behavior. Here we describe the adaptation of an in vitro culture technique of adult brain slices with selected coronal sections, involving the two main brain neurogenic niches, the sub-ventricular zone (SVZ), and the hippocampus dentate gyrus, together with their associated sub-ependymal zone (SEZ). We explain certain examples of the experimental approach to modify neurogenic niche soluble signaling, implanting latex microbeads as a carrier for soluble signals. Additionally, we introduce an immune-cytochemical approach involving bromodeoxyuridine detection as a neural precursor cellular lineage tracer in combination with different molecular expressions, as a means of testing progressive states of neural precursor differentiation and neuronal maturation. This system represents a suitable strategy for evaluating the biological role of soluble components of the adult brain neurogenic niche.

In recent years, the presence of Pharmaceutical Active Compounds (PhACs) in ecosystems has become a serious environmental problem due to their capacity to induce harmful effects at extremely low concentrations in both humans and wildlife. Water treatment plants have not been designed to remove these types of compounds efficiently. Thus, the detection of these pollutants is essential to evaluate their negative impacts and is one of the emerging issues in environmental chemistry. The main objective of this study is to determine the bacterial toxicity of two PhACs (both individually and as a mixture) through the quantification of bioluminescence inhibition in the marine bacteria Aliivibrio fischeri, a commonly used method in short-term toxicity tests. In this work, Acetaminophen and Edaravone, two drugs approved by the Food and Drug Administration, have been studied. The acute toxicity of these PhACs has been tested at two exposure times (5 and 15 min) and different concentrations, by estimation of the median effective concentration (EC50) for each individual compound or in combination at different concentrations. Moreover, the EC50 of the binary mixtures Acetaminophen/Edaravone have been forecast using two traditional predictive models, Concentration Addition and Independent Action. The results show that toxicity decreases with exposure time and depends on the concentration tested. Furthermore, a novel semi-empirical Van Laar-based model has been proposed and validated with the experimental data from this study and literature data, obtaining satisfactory estimations of the EC50 for binary mixtures.