Regenerating cortical connections in a dish: the entorhino-hippocampal organotypic slice co-culture as tool for pharmacological screening of molecules promoting axon regeneration

We present a method for using long-term organotypic slice co-cultures of the entorhino-hippocampal formation to analyze the axon-regenerative properties of a determined compound. The culture method is based on the membrane interphase method, which is easy to perform and is generally reproducible. The degree of axonal regeneration after treatment in lesioned cultures can be seen directly using green fluorescent protein (GFP) transgenic mice or by axon tracing and histological methods. Possible changes in cell morphology after pharmacological treatment can be determined easily by focal in vitro electroporation. The well-preserved cytoarchitectonics in the co-culture facilitate the analysis of identified cells or regenerating axons. The protocol takes up to a month

Historical first descriptions of Cajal-Retzius cells: from pioneer studies to current knowledge

Santiago Ramón y Cajal developed a great body of scientific research during the last decade of 19th century, mainly between 1888 and 1892, when he published more than 30 manuscripts. The neuronal theory, the structure of dendrites and spines, and fine microscopic descriptions of numerous neural circuits are among these studies. In addition, numerous cell types (neuronal and glial) were described by Ramón y Cajal during this time using this 'reazione nera' or Golgi method. Among these neurons were the special cells of the molecular layer of the neocortex. These cells were also termed Cajal cells or Retzius cells by other colleagues. Today these cells are known as Cajal-Retzius cells. From the earliest description, several biological aspects of these fascinating cells have been analyzed (e.g., cell morphology, physiological properties, origin and cellular fate, putative function during cortical development, etc). In this review we will summarize in a temporal basis the emerging knowledge concerning this cell population with specific attention the pioneer studies of Santiago Ramón y Cajal

Potential of microfluidics and lab-on-chip platforms to improve understanding of 'prion-like' protein assembly and behavior

Human aging is accompanied by a relevant increase in age-associated chronic pathologies, including neurodegenerative and metabolic diseases. The appearance and evolution of numerous neurodegenerative diseases is paralleled by the appearance of intracellular and extracellular accumulation of misfolded proteins in affected brains. In addition, recent evidence suggests that most of these amyloid proteins can behave and propagate among neural cells similarly to infective prions. In order to improve understanding of the seeding and spreading processes of these 'prion-like' amyloids, microfluidics and 3D lab-on-chip approaches have been developed as highly valuable tools. These techniques allow us to monitor changes in cellular and molecular processes responsible for amyloid seeding and cell spreading and their parallel effects in neural physiology. Their compatibility with new optical and biochemical techniques and their relative availability have increased interest in them and in their use in numerous laboratories. In addition, recent advances in stem cell research in combination with microfluidic platforms have opened new humanized in vitro models for myriad neurodegenerative diseases affecting different cellular targets of the vascular, muscular, and nervous systems, and glial cells. These new platforms help reduce the use of animal experimentation. They are more reproducible and represent a potential alternative to classical approaches to understanding neurodegeneration. In this review, we summarize recent progress in neurobiological research in 'prion-like' protein using microfluidic and 3D lab-on-chip approaches. These approaches are driven by various fields, including chemistry, biochemistry, and cell biology, and they serve to facilitate the development of more precise human brain models for basic mechanistic studies of cell-to-cell interactions and drug discovery

TrkB signaling is required for postnatal survival of CNS neurons and protects hippocampal and motor neurons from axotomy-induced cell death

Newborn mice carrying targeted mutations in genes encoding neurotrophins or their signaling Trk receptors display severe neuronal deficits in the peripheral nervous system but not in the CNS. In this study, we show that trkB (¿/¿) mice have a significant increase in apoptotic cell death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hippocampus, although elevated levels of pyknotic nuclei were also detected in cortical layers II and III and V and VI, the striatum, and the thalamus. Furthermore, axotomized hippocampal and motor neurons of trkB (¿/¿) mice have significantly lower survival rates than those of wild-type littermates. These results suggest that neurotrophin signaling through TrkB receptors plays a role in the survival of CNS neurons during postnatal development. Moreover, they indicate that TrkB receptor signaling protects subpopulations of CNS neurons from injury- and axotomy-induced cell death

Aceite de semilla de mostaza etíope con alto contenido en ácido oleico

Referencia OEPM: P9902552.-- Fecha de solicitud: 19/11/1999.-- Titular: Consejo Superior de Investigaciones Científicas (CSIC).Aceite de semilla de mostaza etíope con alto contenido en ácido oleico. La presente invención se refiere a un aceite de semilla de mostaza etíope (nombre científico Brassica carinata A.Braun) carente de ácido erúcico (menos de 2% en peso respecto al contenido total en ácidos grasos del aceite) y con un contenido en ácido oleico entre el 60% y el 80% en peso del total de ácidos grasos. Este tipo de aceite no es producido en la naturaleza por plantas de mostaza etíope y ha sido obtenido mediante un procedimiento biotecnológico. El aceite es muy estable frente a la oxidación y las altas temperaturas, lo que hace que sea especialmente indicado en alimentación humana y también en la industria de aceites lubricantes.Peer reviewe

Capacity for seeding and spreading of argyrophilic grain disease in a wild-type murine model; comparisons with primary age-related tauopathy

Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in the limbic system. AGD has a characteristic pattern progressively involving the entorhinal cortex, amygdala, hippocampus, dentate gyrus, presubiculum, subiculum, hypothalamic nuclei, temporal cortex, and neocortex and brainstem, thus suggesting that argyrophilic grain pathology is a natural model of tau propagation. One series of WT mice was unilaterally inoculated in the hippocampus with sarkosyl-insoluble and sarkosyl-soluble fractions from 'pure' AGD at the age of 3 or 7/12 months and killed 3 or 7 months later. Abnormal hyper-phosphorylated tau deposits were found in ipsilateral hippocampal neurons, grains (dots) in the hippocampus, and threads, dots and coiled bodies in the fimbria, as well as the ipsilateral and contralateral corpus callosum. The extension of lesions was wider in animals surviving 7 months compared with those surviving 3 months. Astrocytic inclusions were not observed at any time. Tau deposits were mainly composed of 4Rtau, but also 3Rtau. For comparative purposes, another series of WT mice was inoculated with sarkosyl-insoluble fractions from primary age-related tauopathy (PART), a pure neuronal neurofibrillary tangle 3Rtau + 4Rtau tauopathy involving the deep temporal cortex and limbic system. Abnormal hyper-phosphorylated tau deposits were found in neurons in the ipsilateral hippocampus, coiled bodies and threads in the fimbria, and the ipsilateral and contralateral corpus callosum, which extended with time along the anterior-posterior axis and distant regions such as hypothalamic nuclei and nuclei of the septum when comparing mice surviving 7 months with mice surviving 3 months. Astrocytic inclusions were not observed. Tau deposits were mainly composed of 4Rtau and 3Rtau. These results show the capacity for seeding and spreading of AGD tau and PART tau in the brain of WT mouse, and suggest that characteristics of host tau, in addition to those of inoculated tau, are key to identifying commonalities and differences between human tauopathies and corresponding murine models

Characteristcs of the firm and export performance

Este traballo trata de demostra-la influencia de tres características do perfil das empresas (tamaño, participación do capital estranxeiro e sector de actividade) no seu rendemento exportador, medido a través das variables probabilidade de exportar e propensión exportadora. A utilización da análise de varianza, de regresión (lineal e loxística), log-lineal xerárquico e do algoritmo "CHAlD" permite mostra-la influencia daminante do tamaño da empresa na probabilidade de exportar -o sector determina a probabilidad e de exportar só nas empresas de tamaño máis pequeno-. O considera-la propensión exportadora verificase o impacto prevalecente do sector, con electos diferenciados do tamaño segundo o sector industrial examinado. A participación do capital estranxeiro en ningún caso presenta efectos significativosSome characteristics of the firm such as size, rata of foreign capital or industry could affect export. Linear and logistic regression, variance and log-linear analysis, and CHAlD algorithm have been used to test those relationships. Results have shown that export probability is related to the size of the company. lndustry has only some effects on small and medium-sized enterprises. Export intensity of the firm depends on industry and the relationship between size and export intensity is different in different industries. The influence of foreign trade capital rate cannot be testedS

Role of cellular prion protein in interneuronal amyloid transmission

Several studies have indicated that certain misfolded amyloids composed of tau, β-amyloid or α-synuclein can be transferred from cell to cell, suggesting the contribution of mechanisms reminiscent of those by which infective prions spread through the brain. This process of a 'prion-like' spreading between cells is also relevant as a novel putative therapeutic target that could block the spreading of proteinaceous aggregates throughout the brain which may underlie the progressive nature of neurodegenerative diseases. The relevance of β-amyloid oligomers and cellular prion protein (PrPC) binding has been a focus of interest in Alzheimer's disease (AD). At the molecular level, β-amyloid/PrPC interaction takes place in two differently charged clusters of PrPC. In addition to β-amyloid, participation of PrPC in α-synuclein binding and brain spreading also appears to be relevant in α-synucleopathies. This review summarizes current knowledge about PrPC as a putative receptor for amyloid proteins and the physiological consequences of these interactions

Cortistain is expressed in a distinct subset of cortical interneurons

Cortistatin is a presumptive neuropeptide that shares 11 of its 14 amino acids with somatostatin. In contrast to somatostatin, administration of cortistatin into the rat brain ventricles specifically enhances slow wave sleep, apparently by antagonizing the effects of acetylcholine on cortical excitability. Here we show that preprocortistatin mRNA is expressed in a subset of GABAergic cells in the cortex and hippocampus that partially overlap with those containing somatostatin. A significant percentage of cortistatin-positive neurons is also positive for parvalbumin. In contrast, no colocalization was found between cortistatin and calretinin, cholecystokinin, or vasoactive intestinal peptide. During development there is a transient increase in cortistatin-expressing cells in the second postnatal week in all cortical areas and in the dentate gyrus. A transient expression of preprocortistatin mRNA in the hilar region at P16 is paralleled by electrophysiological changes in dentate granule cells. Together, these observations suggest mechanisms by which cortistatin may regulate cortical activity

Study on the specific capacitance of an activated carbon cloth modified with reduced graphene oxide and polyaniline by cyclic voltammetry

This work describes a two-step process for the electrochemical coating of reduced graphene oxide (RGO) and polyaniline (PANI) onto an activated carbon cloth (ACC) by cyclic voltammetry (CV). The fact that the two syntheses are carried out independently of each other, makes it possible to select the experimental conditions for each one and to study the electrochemical response of RGO, PANI, and PANI onto RGO (RGOPANI), separately. Thus, by modifying the potential limits of the aniline-polymerization reaction, it was possible to observe the influence of RGO and the maximum amount of PANI that the carbon cloth can receive in terms of proper electrochemical response. Electrochemical properties were characterized by CV, galvanostatic charge-discharge curves (using three or two-electrodes symmetric cell configurations) and electrochemical impedance spectroscopy (EIS). A maximum improvement of 25%, 56% and 61% over the initial specific capacitance of ACC (about 129 F g−1) were obtained for RGO, PANI and RGOPANI coatings, respectively. Good cycling stability retaining 83% of the initial capacitance, after 1000 cycles stability test, was obtained for RGOPANI sample. Promising results of energy and power densities were also achieved. In the analyses by Fourier transform infrared spectroscopy (FTIR), the PANI-bands could be clearly identified which is indicative of a significant presence of PANI. Field emission scanning electron microscopy (FESEM) showed the morphology of RGO, PANI and RGOPANI onto the ACC fibers. These analyses helped to explain the electrochemical results.The authors wish to acknowledge to Chemviron Carbon who kindly donated the ZORFLEX (R) activated carbon fabric. The authors wish to thank the Spanish Agenda Estatal de Investigacion (AEI) and European Union (FEDER funds) for the financial support (contract MAT2016-77742-C2-1-P). Tim Vickers is gratefully acknowledged for help with the English revision.Fernández Sáez, J.; Bonastre Cano, JA.; Molina Puerto, J.; Del Río García, AI.; Cases Iborra, FJ. (2017). Study on the specific capacitance of an activated carbon cloth modified with reduced graphene oxide and polyaniline by cyclic voltammetry. European Polymer Journal. 92:194-203. doi:10.1016/j.eurpolymj.2017.04.044S1942039