High sensitivity to carcinogens in the brain of a mouse model of Alzheimer's disease

Cancer and Alzheimer’s disease (AD) are commonly found among elderly patients. Chronic inflammation is the characteristic of both diseases. Amyloid-b peptide is the main inducer of inflammation in AD. Moreover, chronic inflammation promotes cancer, suggesting that AD patients may be more prone to develop cancer than nondemented people. To test this hypothesis, we injected the carcinogen 20-methylcholanthrene in the brain of transgenic mice overexpressing the mutant forms of amyloid precursor protein (APP) and presenilin 1 (PS1), as a model of AD, and their wild-type (WT) littermates. Mutant mice developed tumors faster and with higher incidence than their WT counterparts. Expression of the inflammatory markers interleukin (IL)-1a, IL-1b, IL-6, IP-10 and tumor necrosis factor-a (TNF-a) was measured in AD and WT mice of 3 and 12 months of age that had not been exposed to the carcinogen. These cytokines were elevated in older AD mice, indicating the existence of a highly inflammatory milieu in these animals. We also found elevated expression of a mutated form of p53 in older AD mice, suggesting an alternative mechanism for the predisposition of AD brains to develop brain tumors. Clinical studies reporting comorbidity of AD and brain cancer are needed to understand whether our observations hold true for humans.This work was supported by Spanish Ministry of Science and Innovation Grant SAF2007-60010, and Instituto de Salud Carlos III Grant RD06/0026/1001.Peer reviewe

Cajal´s achievements in the field of the development of dendritic arbors

13 páginas, 7 figuras.In 1909, Cajal published an up-dated version in French (Cajal, 1909-1911) of his main work Texture of the Nervous System of Man and Vertebrates (Cajal, 1899-1904), considered the most important book devoted to the nervous system. Owing that last year was the centenary of this publication, we decided to produce an article focused on Cajal´s description of the morphological changes that dendritic trees undergo during development. We will emphasize his brilliant hypotheses explaining the modelling of dendritic trees (the neurotropic hypothesis and the role of neuronal activity in the patterning of the dendritic trees), and the status of this topic in present day Neuroscience. Here, we will show original photographs taken from a selected collection of Cajal´s slides housed in the Cajal Museum (Instituto Cajal, CSIC, Madrid, Spain) illustrating the principal changes in neuronal morphology at different stages of development of the spinal cord, cerebellum and cerebral cortex. We will also discuss Cajal’s initial proposals regarding the influence of neurotropic substances (chemotactic hypothesis) and neural activity in the modelling of the dendritic tree, as well as the evidence that later confirmed these theories.P. GL. is supported by the Fundación Caixa Galicia. This study was supported by grants from Spain´s Ministry of Science and Innovation (SAF2007- 60010) and the Instituto de Salud Carlos III (RETICS, RENEVAS, RD06/ 0026/1001).Peer reviewe

Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury

Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I) in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. The protection mediated by IGF-I against oxidative stress (H2O2) in astrocytes is probably needed for these cells to provide adequate neuroprotection. Indeed, in astrocytes but not in neurons, IGF-I helps decrease the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H2O2 such as stem cell factor (SCF) to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging

Cambios de uso y dinámica ecogeomorfológica en las unidades de paisaje del Parque Natural y Geoparque Sierras Subbéticas (provincia de Córdoba).

El Parque Natural y Geoparque Sierras Subbéticas es un espacio de gran valor por su patrimonio geológico y biológico, pero también cultural. Este trabajo realiza un análisis de la dinámica espacial y temporal de sus usos, coberturas vegetales y superficie del suelo en las unidades de paisaje de dicho espacio. Para ello, se aplican procedimientos cartográficos y de análisis de imágenes de satélites mediante Tecnologías de Información Geográfica. Como resultados principales destacan: i) el área de estudio queda dividida en cuatro unidades de paisaje; ii) estas han mostrado cambios a largo plazo semejantes a otras áreas de montaña mediterránea: abandono de cultivos y renaturalización del espacio: y iii) a corto-medio plazo, la cubierta vegetal y las condiciones superficiales de los suelos reflejan el impacto intra e inter-anual de la variabilidad climática mediterránea, además de otro de índole inducida, como el fuego. Estos resultados ofrecen la posibilidad de avanzar hacia una delimitación de áreas de diferente resiliencia frente al impacto del cambio climático, para dotar a los gestores del parque natural de información y herramientas adecuadas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury

Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I) in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. The protection mediated by IGF-I against oxidative stress (H 2O 2) in astrocytes is probably needed for these cells to provide adequate neuroprotection. Indeed, in astrocytes but not in neurons, IGF-I helps decrease the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H 2O 2 such as stem cell factor (SCF) to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging. © 2014 Genis L et al.This work was funded by grants of the Spanish Ministry of Science (SAF2010-17036) and Centro Investigacion Biomedica en red Enfermedades Neurodegenerativas (CIBERNED) to IT-A.Peer Reviewe

Neurorrestauración tras la isquemia cerebral: papel de los neurotransmisores en la neurogénesis postisquémica

Introduction. Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. Development. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Conclusion. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.Peer Reviewe

Fragilité visuelle des paysages associée á la dynamique temporelle des champs de châtaigniers dans la municipalité de Faraján (Espagne)

The study is carried out in a mountainous area from South of Spain (Faraján, province of Málaga). The landscape shows a very high spatially and temporally dynamic of land uses, similar to other Mediterranean mountainous regions, where interacts physical and human factors. The land uses and vegetation cover, and especially the chestnut orchards, were mapped by means of supervised classification of Landsat 8-OLI images and aerial photographs. This land use has a remarkable impact on the landscape and local economy due to the seasonal variability of chestnut tree phenology and its profitability. As consequence, the landscape visual fragility is analysed in order to assess the impact of land use changes as well as the increment of the surface occupied by the chestnut orchard land use, which is prone to spread all over the highest altitude of the Faraján municipality from recent decades and, thus, along the the most visible areas from the main roads.Este trabajo se lleva a cabo en un área de montaña de la provincia de Málaga (municipio de Faraján), en el sur de España. En dicho municipio, el paisaje muestra una dinámica territorial e histórica semejante a la de otros espacios de montaña mediterránea, coexistiendo e interactuando factores físico-naturales y antrópicos que lo hacen muy variable en el espacio y el tiempo. Mediante la clasificación supervisada de imágenes Landsat 8-OLI y la foto-interpretación de imágenes aéreas, se obtuvieron los mapas de usos del suelo y cobertura vegetal a fin caracterizar su dinámica espacio-temporal, con especial atención en el cultivo de castaño. Este cultivo, dada sus variaciones estacionales, introduce a su vez un fuerte dinamismo en el paisaje del municipio, cuya riqueza y belleza es notable. Por ello, se analiza la fragilidad visual de este paisaje y los efectos que en él pueden tener los cambios de uso, en general y el incremento en la superficie ocupada por los campos de castaños, en particular, que tiende a situarse en las áreas más visibles del municipio desde las principales vías de comunicación de su entorno.Ce travail est effectué dans une zone de montagne dans la province de Málaga (municipalité de Faraján), dans le sud de l’Espagne. Là, le paysage présente une dynamique territoriale et historique semblable à celle des autres régions de la montagne méditerranéenne, où des facteurs naturels et humains coexistent et interagissent pour créer des paysages très variables dans l’espace et le temps. Grâce à la classification supervisée des images Landsat 8-OLI et photo-interprétation d’images aériennes, des cartes de l’utilisation des sols et surfaces vegetées pour caractériser la dynamique spatio-temporelle, avec une attention particulière à la culture du châtaignier ont été obtenues. Cette culture, compte tenu de ses variations saisonnières, introduit à son tour un fort dynamisme dans le paysage de la municipalité, dont la richesse et la beauté est remarquable. Par conséquent, la fragilité visuelle de ce paysage et les effets que sur elle peut avoir des changements dans l’utilisation et l’augmentation de la superficie occupée par des champs de châtaigniers sont analysés. Ils ont tendance à être placés dans les zones les plus visibles de la municipalité des routes principales dans cet environnement

Biogeographical affinities of fish associated to the shrimp trawl fishery in the Gulf of Tehuantepec, Mexic

18 pages, 2 figures, 2 tables[EN] Fish by-catch of the Gulf of Tehuantepec shrimp fishery is mainly composed of several species that are discarded in their majority. Fish by-catch species composition, distribution and biogeographical affinities were analyzed through 15 cruises carried on the continental shelf at a depth of 12 to 70 m during 2003, 2004, 2005 and 2013. Fish by-catch was represented by 58 families, 129 genera and 242 species. The families Haemulidae, Sciaenidae, Paralichthyidae, Gerreidae and Carangidae accounted for >70% of the catch. Haemulopsis axillaris, Syacium ovale, Selene peruviana, Diapterus peruvianus, Larimus acclivins and Stellifer erycimba were the most frequent species at <40 m depth (inner shelf), and Prionotus stephanophrys, Scorpaena russula, Porichthys analis and Synodus scituliceps were dominant at 40−60 m depth (outer shelf). Analysis of biogeographical affinities showed that 36.1% of species had a wide distribution, from San Diego Province to the Panamic Province, while 13.2% had a restricted distribution in the Mexican and Panamic Provinces. The ichthyofaunal composition was markedly influenced by the local environment and seasonal conditions[ES] En la pesquería del camarón del Golfo de Tehuantepec un gran número de especies de peces se capturan como fauna de acompañamiento y son descartadas. La composición, distribución y afinidades biogeográficas de la ictiofauna acompañante del camarón fue analizada mediante 15 cruceros desarrollados en la plataforma continental entre 15-64 m de profundidad durante 2003, 2004, 2005 y 2013. La ictiofauna descartada estuvo representada por 58 familias, 129 géneros y 242 especies. Las familias, Haemulidae, Sciaenidae, Paralichthyidae, Gerreidae y Carangidae aportaron más del 70 % de la captura. Haemulopsis axillaris, Syacium ovale, Selene peruviana, Diapterus peruvianus, Larimus acclivins y Stellifer erycimba fueron las especies más frecuentes en profundidades menores de 40 m (plataforma interna), mientras que Prionotus stephanophrys, Scorpaena russula, Porichthys analis y Synodus scituliceps, fueron dominantes entre 40-60 m de profundidad 698 (plataforma externa). El análisis de las afinidades biogeográficas mostró que el 36.1 % de las especies son de amplia distribución desde la provincia de San Diego a la Panámica, mientras que el 13.2 %, presentó una distribución restringida entre la provincia Mexicana y la Panámica. La composición de la ictiofauna estuvo marcadamente influenciada por las condiciones ambientales locales y sus variaciones estacionalesThis study was partially supported by the Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (PAPIIT), Grant IN211214-2Peer Reviewe

Santiago Ramón y Cajal: un modelo de excelencia para desarrollar competencias en el Grado en Medicina

El presente proyecto ha acercado la figura de Santiago Ramón y Cajal a los estudiantes de Medicina como estrategia para el desarrollo de competencias generales, específicas y transversales necesarias para la formación de profesionales competentes. Se han realizado una serie de actividades en torno a nuestro Premio Nobel que han involucrado a docentes, investigadores y clínicos

ASS234, as a new Multi-Target Directed propargylamine for Alzheimer’s disease therapy

MU and JMC thank MINECO (Spain) for support (Grant SAF2012-33304; SAF2015-65586-R). RRR, MU, GE and JMC thank EU (COST Action 1103) for support.The complex nature of Alzheimer’s disease (AD) has prompted the design of Multi-Target-Directed Ligands (MTDL) able to bind to diverse biochemical targets involved in the progress and development of the disease. In this context, we have designed a number of MTD propargylamines showing antioxidant, anti-betaamyloid, anti-inflammatory, as well as cholinesterase and monoamine oxidase inhibition capacities. Here, we describe these properties in the MTDL ASS234, our lead-compound ready to enter in pre-clinical studies for AD, as a new multipotent, permeable cholinesterase/monoamine oxidase inhibitor, able to inhibit Aβ- aggregation, possessing antioxidant and neuroprotective properties.Publisher PDFPeer reviewe