Reduction of adult hippocampal neurogenesis modifies brain functional connectivity and enhances cocaine-seeking in mice

Recently, adult hippocampal neurogenesis has been proposed as a putative neuroplastic mechanism involved in those behavioural processes. In this work, we studied the effect of the inhibition of adult hippocampal neurogenesis using the DNA alkylating agent temozolomide (TMZ), in cocaine-induced conditioned place preference (CPP) behaviour. In a first experiment, we investigated both CPP acquisition/expression and the functional brain circuits underlying CPP expression in control and neurogenesis-reduced conditions by analysing c-Fos immunoreactivity (c-Fos IR) in hippocampal and extrahippocampal addiction-related areas. A second experiment was designed to study the involvement of adult-born neurons in the extinction and cocaine-induced reinstatement of drug-seeking in the CPP model. We performed two independent studies where adult hippocampal neurogenesis was inhibited either before or after the CPP was acquired. Our results showed that TMZ treatment had no effect on the acquisition of the cocaine-induced CPP, but c-Fos IR associated to the test trial (CPP expression) revealed an increased activity in some of the analysed brain areas in the CPP-TMZ mice. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain network associated with CPP expression. However, mice with reduced neurogenesis showed an alternative brain circuit. The results of the second experiment revealed that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug seeking behaviour. However, when neurogenesis was inhibited after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that the role of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition.Universidad de Málaga. Andalucía Tech, Campus de Excelencia Internacional. Spanish Ministry of Economy and Competitiveness (PSI2013-44901-P to L.J.S.; Subprograma RETICS Red de Trastornos Adictivos RD12/0028/0001, to F.R.F.). Author E.C-O. holds a ‘Sara Borrell’ research contract from the Spanish Carlos III Health Institute, Spanish Ministry of Economy and Competitiviness (grant number CD12/00455). Author D.L.G-M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (grant number FPU13/04819)

Aproximación a las representaciones sociales sobre los pueblos de la Costa Caribe en el discurso periodístico de El Nuevo Diario.

Conocer y vivir la Costa Caribe nicaragüense es un reto que dejamos a nuestros lectores. En el presente trabajo encontrará los resultados de la investigación “Aproximación a las representaciones sociales sobre los pueblos de la Costa Caribe en el discurso periodístico de El Nuevo Diario”. El estudio de carácter cualitativo se realizó durante los meses de enero, febrero y marzo del 2014, año en el que las comunidades caribeñas eligieron a sus concejeros de los Gobiernos Regionales, autoridades que son reconocidas en el Estatuto de Autonomía de los Pueblos de la Costa Caribe mismo que fue aprobado en octubre de 1987. La investigación analizó las representaciones sociales construidas sobre los pueblos de la Costa Caribe de Nicaragua desde el que hacer informativo del El Nuevo Diario en el primer trimestre del año 2014, tiempo en el que se incluyeron para análisis todas las noticias referidas al Caribe y Alto Wangki que fueron publicadas en las Secciones: Portada, De Portada, Nacionales, Política, Opinión, Revista, Deportes, Dinero y Fama. La investigación que busca aportar al cambio, a que los comunicadores regionales y nacionales desde sus narrativas ayuden a la construcción de una nación multiétnica y juntos derriben las brechas comunicacionales que han impuesto los grandes medios de comunicación. Con la investigación se conoció la agenda informativa de El Nuevo Diario, cómo se habla y quiénes hablan por ellos, qué temas son los que se publican sobre los pueblos de la costa Caribe y cuántas veces se habla de los costeños. En el tiempo de investigación se revisaron las noventa publicaciones de END, tiempo en el que publicaron 101 noticias referidas al Caribe, de estas publicaciones 62 notas informaban sobre los problemas de tierra, los comicios electorales que se desarrollaban en el Caribe, 19 están relacionadas a los problemas de infraestructura social que faltan o se construyen en las regiones, en las otras 20 noticias se presentaron los problemas de inseguridad ciudadana que se vive en las regiones autónomas

D-chiro-inositol prevents memory deficits in the 3xTg mouse model of Alzheimer’s disease in a sex-dependent manner.

Subida por la tutora, a petición de Beatriz Pacheco Sánchez.Alzheimer’s disease (AD) is recognized as an age-related neurodegenerative disorder, characterized by the aggregation and deposition of amyloid-β (Aβ) in plaques and neurofibrillary tangles (NFTs) composed of aggregates of hyperphosphorylated tau, a microtubule-associated protein. Sporadic AD, the most prevalent form of the disease, has been proposed to be associated with alterations on insulin signaling. Insulin regulates a series of cognitive processes, such as learning and memory formation and emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of neurodegeneration, particularly in AD. The present study describes the effect of oral dietary administration of D-Chiro-inositol (DCI), an inositol used against insulin resistance, on the occurrence of the cognitive impairment of 3xTg-AD mice. This so called “triple‐ transgenic mice” model mimics many critical aspects of AD neuropathology. To this end, we analysed the effects of daily oral administration DCI 200 mg/Kg/day in male and female 3xTg and WT mice of 9 and 3 months of age. In addition to the evaluation of memory on the Novel Object Recognition, both the locomotion and time in the centre zone of an open field (OF), and the locomotion and anxiety-like behaviour in the elevated plus maze (EPM) test, were monitored. Our results showed that the exploration time of the new object was remarkably higher in the male 3xTg-DCI group when compared to those obtained from the 3xTg-vehicle and WT- vehicle groups at a middle and older age (3 and 9 months). When the center exploration time was analyzed in OPF test, three-way ANOVA showed an effect of the genotype in middle-aged animals. In the EPM test, only 9 months old 3xtg-DCI females were more prone to explore the open-arm, suggesting DCI decreases anxiety levels related to AD. In conclusion, our study suggest that DCI prevents and improves in a sex-dependent manner, the cognitive impairment associated to AD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Marine nematode taxonomy in the DNA age: the present and future of molecular tools to access their biodiversity

Molecular taxonomy is one of the most promising yet challenging fields of biology. Molecular markers such as nuclear and mitochondrial genes are being used in a variety of studies surveying marine nematode taxa. Sequences from more than 600 species have been deposited to date in online databases. These barcode sequences are assigned to 150 nominal species from 104 genera. There are 41 species assigned to Enoplea and 109 species to Chromadorea. Morphology-based surveys are greatly limited by processing speed, while barcoding approaches for nematodes are hampered by difficulties in matching sequence data with morphology-based taxonomy. DNA barcoding is a promising approach because some genes contain variable regions that are useful to discriminate species boundaries, discover cryptic species, quantify biodiversity and analyse phylogeny. We advocate a combination of several approaches in studies of molecular taxonomy, DNA barcoding and conventional taxonomy as a necessary step to enhance the knowledge of biodiversity of marine nematodes

Persistent changes in exploration and hyperactivity coexist with cognitive impairment in mice withdrawn from chronic cocaine

Repeated cocaine exposure induces lasting neurobehavioral adaptations such as cognitive decline in animal models. However, persistent changes in spontaneous –unconditioned- motor and exploratory responses are scarcely reported. In this study, mice were administered with cocaine (20 mg/kg/day) or vehicle for 12 consecutive days. After 24 days of drug abstinence, a behavioral assessment was carried out in drug-free conditions and in unfamiliar environments (i.e. no cocaine-associated cues were presented). The cocaine-withdrawn mice showed cognitive deficits in spontaneous alternation behavior and place recognition memory. Importantly, they also displayed hyperlocomotion, increased rearing activity and altered exploratory patterns in different tasks. In the forced swimming test, they were more active (struggled/climbed more) when trying to escape from the water albeit showing normal immobility behavior. In conclusion, in addition to cognitive deficits, chronic cocaine in rodents may induce long-lasting alterations in exploratory activity and psychomotor activation that are triggered even in absence of drug-related stimuli.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigación –AEI-) cofounded by the European Regional Development Fund-FEDER, UE- (PSI2015–73,156-JIN to E.C–O.; PSI2017–82604R to L.J.S.), RETICS Red de Trastornos Adictivos (ERDF-EU; RD16/0017/0001 to F.R.F.) and University of Málaga (B4: ‘Ayudas para Proyectos Puente’to E.C–O). Funding for open access charge: Universidad de Málaga /CBUA. Authors M.C.M-P., F. A-G. and S. G-R. hold predoctoral grants from the Spanish Ministry of Science, Innovation and Universities (FPU17/00276 to M.C.M-P.; PRE2018–085673 to F.A-G.; and FPU18/00941 to S.G-R.). Author D.L.G.M. holds a postdoctoral grant from University of Málaga (A.3. Plan Propio de Investigación y Transferencia Universidad de Málaga)

Femtosecond two-photon absorption spectroscopy of poly(fluorene) derivatives containing benzoselenadiazole and benzothiadiazole

We have investigated the molecular structure and two-photon absorption (2PA) properties relationship of two push-pull poly(fluorene) derivatives containing benzoselenadiazole and benzothiadiazole units. For that, we have used the femtosecond wavelength-tunable Z-scan technique with a low repetition rate (1 kHz) and an energy per pulse on the order of nJ. Our results show that both 2PA spectra present a strong 2PA (around 600 GM (1 GM = 1×10-50 cm4 .s. photon-1)) band at around 720 nm (transition energy 3.45 eV) ascribed to the strongly 2PA-allowed 1Ag-like → mAg-like transition, characteristic of poly(fluorene) derivatives. Another 2PA band related to the intramolecular charge transfer was also observed at around 900 nm (transition energy 2.75 eV). In both 2PA bands, we found higher 2PA cross-section values for the poly(fluorene) containing benzothiadiazole unit. This outcome was explained through the higher charge redistribution at the excited state caused by the benzothiadiazole group as compared to the benzoselenadiazole and confirmed by means of solvatochromic Stokes shift measurements. To shed more light on these results, we employed the sum-over-states approach within the two-energy level model to estimate the maximum permanent dipole moment change related to the intramolecular charge transfer transition

LH-21, a CB1 antagonist, reduces hepatotoxic damage produced by paracetamol overdose in a mice model.

Drug-induced liver injury (DILI) is one of the main causes of hepatic acute failure. Paracetamol can cause it when is ingested in excessive doses, leading to the depletion of the antioxidant mechanisms of the hepatocytes and a series of processes that conclude with cell death. One of the altered metabolic pathways is the endocannabinoid system (ECS), which has become a very interesting target to alleviate these events due to its involvement in inflammatory processes. For this reason, the triazole-derived compound LH-21, a cannabinoid receptor Cb1 antagonist, was used for the treatment of DILI in 8-week-old male C57BL/6 mice. In the present study, fasting mice were subjected to an oral overdose of paracetamol (300 mg/kg) and treated 2 hours later with 3 mg/kg of LH-21. After 24 hours, the animals were sacrificed and the livers were collected to determine the hepatic levels of metabolites related to antioxidant mechanisms, the expression of proteins involved in the generation of cellular damage and the transcription grade of the different components of the ECS. The observed results showed that LH-21 treatment raises GSH levels and total antioxidant capacity, in addition to reducing malondialdehyde values. Furthermore, the phosphorylation degree of Jnk and Stat3, as well as the activation status of Casp3, diminished. Regarding the ECS, the expression of Ppara, Cnr1, Cnr2 and Gpr55 did return to normal levels. This suggests that LH-21 effectively blocks the Cb1 activity, allowing the correct function of Ppar-α that promotes a cellular anti-inflammatory state and the relief of the symptoms produced by DILI. These results exhibit a promising perspective for the prevention or treatment of some toxic effects of paracetamol overdose with LH-21. Nevertheless, these findings are a first step to continue studying the involvement of the ECS in this type of liver disease and investigating the effectiveness of this Cb1 antagonist against the pathophysiology of DILI.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Neuroplastic and cognitive impairment in substance use disorders: a therapeutic potential of cognitive stimulation

Author manuscriptDrug addiction is a chronic and relapsing disorder in which repeated drug exposure compromises brain neuroplasticity. Brain areas normally involved in learning and goal- directed behaviors become corrupted, which may lead to cognitive deficits that coexist with other addiction symptoms and predict a worse treatment outcome. New learning experiences that are not motivated by drugs may improve both cognitive deficits and drug-induced symptoms by promoting adaptive neuroplastic changes that could alleviate or reverse those involved in addiction. The present review will focus on whether potentiating healthy cognitive function, either by formal cognitive training or non-drug related environmental experiences, could exert beneficial effects in the therapeutics of addiction. Although additional studies are needed, the available clinical and preclinical evidence suggests that cognitive stimulation may provide a valuable adjuvant intervention in drug addiction.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-founded by the European Research Development Fund-AEI/FEDER, UE- (PSI2015-73156-JIN to E.C.O.; PSI2017-82604R to L.J.S.), Red de Trastornos Adictivos (RD16/0017/0001 to F.R.F.), Plan Nacional sobre Drogas, Ministerio de Sanidad, Servicios Sociales e Igualdad (PNSD2015/047 to J.S.) and the University of Málaga (Plan Propio 2017 – ‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to P.S.P). Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of Economy, Industry and Competitiveness (code: FJCI-2015-23925). Author D.L.G.M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (code: FPU13/04819). Authors J.S., A.S. and F.J.P. hold ‘Miguel Servet’ grants (codes: CPII17/00024, CP14/00173 and CP14/00212, respectively) from the National System of Health-Instituto de Salud Carlos- III co-funded by FEDER, UE. Author E.C.O. holds a ‘Jóvenes Investigadores’ grant (code: PSI2015-73156-JIN) from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-funded by FEDER, UE

First-Order Hyperpolarizability Of Triphenylamine Derivatives Containing Cyanopyridine: Molecular Branching Effect

In the present work, we report the multibranching effect on the dynamic first-order hyperpolarizability (β(-2ω; ω, ω)) of triphenylamine derivatives containing cyanopyridine one-branch (dipolar structure), two-branch (V-shaped structure), and three-branch (octupolar structure) structures. For this study, we used the hyper-Rayleigh scattering (HRS) technique involving picosecond pulse trains at 1064 nm. Our results show that βHRS increases from 2.02 × 10-28 to 9.24 × 10-28 cm5/esu when an extra branch is added to the molecule, configuring a change from a dipolar to a V-shaped (quadrupolar) molecular structure. When a third branch is added, leading to an octupolar structure, a decrease to 3.21 × 10-28 cm5/esu is observed. Such a significant decrease in βHRS is attributed to a negative contribution presented in the βHRS description by using a three-level energy approach due to their electronic structure and considering a specific combination of the angle between the dipole moments. On the other hand, the enhancement of βHRS found for the quadrupolar structure is associated with the cooperative enhancement due to the electronic coupling between the branches that increases considerably the transition dipole moment and permanent dipole moment change. To explain the βHRS results obtained for different molecules, we employed the HRS figure of merit, FOMHRS = βHRS/Neff 3/2, in which Neff is the effective number of π-conjugated bonds, and the few-energy level approach for βHRS within the Frenkel exciton model. To shed more light on the experimental results interpretation, we performed time-dependent density functional theory calculations combined with a polarizable continuum model to confirm the energy and oscillator strength of the electronic transitions assumed in the Frenkel exciton model employed here

Identifying Prognostic Factors for Well-Differentiated Metastatic Pancreatic Neuroendocrine Tumours: A Retrospective International Multicentre Cohort Study

Pancreatic neuroendocrine tumours (pNETs) represent rare neoplasms of all NETs often presenting without functional activity. Many sporadic non-functioning pNET patients are already metastatic at the time of diagnosis, and the therapeutic approach to such patients is mostly palliative. In this international, multicentre, retrospective cohort study, we assessed the prognostic value of a set of anthropometric, clinical, biochemical, radiological and pathological parameters at baseline and the impact of the therapeutic strategies on the survival of patients with sporadic grade 1/2, stage IV, non-functioning pNETs. Three hundred and twelve consecutive patients diagnosed between 1993 and 2010 were included. The median overall survival (OS) was 6.6 years and survival at 5 and 10 years was 62 and 34% respectively. On univariate analysis, Eastern Cooperative Oncology Group (ECOG) status > 2, grade 2, bilobar hepatic metastases, synchronous metastases, and high chromogranin A, alkalinephosphatase and lactic-dehydrogenase were associated with a significant reduction of OS. Palliative/curative surgery and loco-regional hepatic interventions were significant factors improving OS. On multivariate analysis, ECOG status >= 2, synchronous metastases, Ki-67 >= 10%, and high alkalinephosphatase correlated significantly with an increased risk of death. Both palliative/curative surgery and loco-regional hepatic interventions had a positive impact on OS. Although most parameters did not prove to be independent OS predictors at multivariate analysis, they showed a tendency towards that. Future prospective studies including larger patient populations may give greater clarity. We believe the integration of these parameters has the potential to provide a reliable prognostic score for the stratification of patients with sporadic well-differentiated metastatic non-functioning pNETs