Leve diferenciación genética entre los límites occidental y oriental de distribución de Astroides calycularis (Pallas, 1776) (Anthozoa, Scleractinia, Dendrophylliidae), inferida a partir de secuencias de COI e ITS

Understanding population genetic structure and differentiation among populations is useful for the elaboration of management and conservation plans of threatened species. In this study, we use nuclear and mitochondrial markers (internal transcribed spacers -ITS and cytochrome oxidase subunit one -COI) for phylogenetics and nested clade analyses (NCA), thus providing the first assessment of the genetic structure of the threatened Mediterranean coral Astroides calycularis (Pallas, 1766), based on samples from 12 localities along its geographic distribution range. Overall, we found no population differentiation in the westernmost region of the Mediterranean; however, a slight differentiation was observed when comparing this region with the Tyrrhenian and Algerian basins.El estudio de la estructura de las poblaciones y su diferenciación a nivel genético es de gran utilidad para la elaboración de planes de manejo y conservación de especies amenazadas. En este estudio, utilizamos marcadores nucleares y mitocondriales (espaciadores internos de genes ribosomales -ITS y citocromo oxidasa, subunidad I -COI) y métodos de análisis filogenéticos y de clados anidados (NCA), para realizar la primera valoración de la estructura genética del coral naranja Astroides calycularis (Pallas, 1766), una especie amenazada del Mediterráneo, a partir de muestras de 12 localidades a lo largo de su área de distribución. En las localidades situadas en la región más occidental del Mediterráneo se encontró cierta homogeneidad genética, mientras que al comparar estas localidades con las de las cuencas argelina y del mar Tirreno se observó una ligera diferenciación

Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration

Alterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer’s disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown. We used a high-fat/high-cholesterol diet in mice to study the effects of hypercholesterolemia over the alarmin S100A8 cascade in the hippocampus. Using CYP27Tg, a transgenic mouse model, we show that the hypercholesterolemia influence on the brain is mediated by the excess of 27-hydroxycholesterol (27-OH), a cholesterol metabolite. We also employed an acute model of 27-OH intraventricular injection in the brain to study RAGE and S100A8 response. We used primary cultures of neurons and astrocytes to study the effect of high levels of 27-OH over the S100A8 alarmin cascade. We report that a high-fat/high-cholesterol diet leads to an increase in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects of hypercholesterolemia to the brain via alarmin signaling.Open access funding provided by Karolinska Institute. This research was supported by the following Swedish foundations: Swedish Brain Power, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, Strategic Neuroscience Program, Margaretha af Ugglas Foundation, Gun och Bertil Stohnes Stiftelse, Karolinska Institutet fund for geriatric research, Stiftelsen Gamla Tjänarinnor, Demensfonden,Lindhés Advokatbyrå, Hjärnfonden, and Alzheimerfonden. R. L.-V. was fnancially supported by Mexico’s National Council for Science and Technology (CONACYT) CVU, 209252, and by Olle Enqvist Foundation grant no. 2014/778. Ramon Areces Foundation, Spain, supported E. P., EMBO Long-Term Fellowship (ALTF 696–2013), the SSMF postdoctoral fellowship, and Juan de la Cierva-Incorporación. (IJCI-2016–27,658) supported P. M.-S

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation

Tau mislocation in glucocorticoid-triggered hippocampal pathology

The exposure to high glucocorticoids (GC) triggers neuronal atrophy and cognitive deficits, but the exact cellular mechanisms underlying the GC-associated dendritic remodeling and spine loss are still poorly understood. Previous studies have implicated sustained GC elevations in neurodegenerative mechanisms through GC-evoked hyperphosphorylation of the cytoskeletal protein Tau while Tau mislocation has recently been proposed as relevant in Alzheimer's disease (AD) pathology. In light of the dual cytoplasmic and synaptic role of Tau, this study monitored the impact of prolonged GC treatment on Tau intracellular localization and its phosphorylation status in different cellular compartments. We demonstrate, both by biochemical and ultrastructural analysis, that GC administration led to cytosolic and dendritic Tau accumulation in rat hippocampus, and triggered Tau hyperphosphorylation in epitopes related to its malfunction (Ser396/404) and cytoskeletal pathology (e.g., Thr231 and Ser262). In addition, we show, for the first time, that chronic GC administration also increased Tau levels in synaptic compartment; however, at the synapse, there was an increase in phosphorylation of Ser396/404, but a decrease of Thr231. These GC-triggered Tau changes were paralleled by reduced levels of synaptic scaffolding proteins such as PSD-95 and Shank proteins as well as reduced dendritic branching and spine loss. These in vivo findings add to our limited knowledge about the underlying mechanisms of GC-evoked synaptic atrophy and neuronal disconnection implicating Tau missorting in mechanism(s) of synaptic damage, beyond AD pathology.We would like to thank Rui Fernandes for TEM technical support. IS was supported by the Portuguese Foundation for Science and Technology (FCT).This work was funded by the Portuguese Foundation for Science and Technology (FCT) (grant NMC-113934 to IS and grant SFRH/BPD/80118/2011 to JC), Canon Foundation and project DoIT - Desenvolvimento e Operacionalização da Investigação de Translação (N° do projeto 13853), funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through the Programa Operacional Fatores de Competitividade (POFC).info:eu-repo/semantics/publishedVersio

Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement

A small peptide from a neuronal cell adhesion molecule enhances synaptic plasticity in the hippocampus and results in improved cognitive performance in rats

Leve diferenciación genética entre los límites occidental y oriental de distribución de Astroides calycularis (Pallas, 1776) (Anthozoa, Scleractinia, Dendrophylliidae), inferida a partir de secuencias de COI e ITS

[EN] This adaptation text reproduces chapter II of the dissertation “Results”: Estudio genético de la estructura poblacional y conectividad de dos corales endémicos del Mediterráneo: Astroides calycularis (Pallas, 1766) y Cladocora caespitosa (Linnaeus, 1767)= Genetic assessment of population structure and connectivity in two endemic Mediterranean corals: Astroides calycularis (Pallas, 1766) and Cladocora caespitosa (Linnaeus, 1767), of P. Casado-Amezúa (2012). http://hdl.handle.net/10261/134913[ES] Este artículo es una adaptación del capítulo II de “Resultados” de la tesis doctoral: Estudio genético de la estructura poblacional y conectividad de dos corales endémicos del Mediterráneo: Astroides calycularis (Pallas, 1766) y Cladocora caespitosa (Linnaeus, 1767)= Genetic assessment of population structure and connectivity in two endemic Mediterranean corals: Astroides calycularis (Pallas, 1766) and Cladocora caespitosa (Linnaeus, 1767), of P. Casado-Amezúa (2012). http://hdl.handle.net/10261/134913[EN] Understanding population genetic structure and differentiation among populations is useful for the elaboration of management and conservation plans of threatened species. In this study, we use nuclear and mitochondrial markers (internal transcribed spacers -ITS and cytochrome oxidase subunit one -COI) for phylogenetics and nested clade analyses (NCA), thus providing the first assessment of the genetic structure of the threatened Mediterranean coral Astroides calycularis (Pallas, 1766), based on samples from 12 localities along its geographic distribution range. Overall, we found no population differentiation in the westernmost region of the Mediterranean; however, a slight differentiation was observed when comparing this region with the Tyrrhenian and Algerian basins.[ES] El estudio de la estructura de las poblaciones y su diferenciación a nivel genético es de gran utilidad para la elaboración de planes de manejo y conservación de especies amenazadas. En este estudio, utilizamos marcadores nucleares y mitocondriales (espaciadores internos de genes ribosomales -ITS y citocromo oxidasa, subunidad I -COI) y métodos de análisis filogenéticos y de clados anidados (NCA), para realizar la primera valoración de la estructura genética del coral naranja Astroides calycularis (Pallas, 1766), una especie amenazada del Mediterráneo, a partir de muestras de 12 localidades a lo largo de su área de distribución. En las localidades situadas en la región más occidental del Mediterráneo se encontró cierta homogeneidad genética, mientras que al comparar estas localidades con las de las cuencas argelina y del mar Tirreno se observó una ligera diferenciación.This study was supported by the BBVA Foundation, the Spanish Ministry of Science and Innovation (CTM2008-00496/MAR and CGL2011-23306) and the “Organismo Autónomo Parques Nacionales”.Peer Reviewe

Combination of Apolipoprotein E4 and High Carbohydrate Diet Reduces Hippocampal BDNF and Arc Levels and Impairs Memory in Young Mice.

The presence of the E4 allele of apolipoprotein E (apoE) is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD). Other risk factors for developing AD have been identified, including lifestyle such as dietary habits. The present study was designed to explore the impact of the interaction between variant human apoE isoforms and a high carbohydrate diet (HCD) on mechanisms behind learning and memory retention. As an investigative model, we compared young apoE3 and apoE4 target replacement mice fed on a HCD for 6 months. Our results indicate that HCD compromises memory processes in apoE4 mice. ApoE4 mice on HCD showed decreased activity-regulated cytoskeletal-associated protein (Arc) and brain derived neurotrophic factor (BDNF) levels, as well as decreased BDNF signaling in the hippocampus. In contrast, apoE3 mice were resistant to the deleterious effects of HCD on both behavior and memory-related proteins. Our results support the hypothesis that already in mid-life, genetic, and environmental risk factors act together on the mechanisms behind cognitive impairment