Cannabinoid control of hippocampal functions: thewherematters

In the brain, hippocampal circuits are crucial for cognitive performance (e.g., memory) and deeply affected in pathological conditions (e.g., epilepsy, Alzheimer). Specialized molecular mechanisms regulate different cell types underlying hippocampal circuitries functions. Among them, cannabinoid receptors exhibit various roles depending on the cell type (e.g., neuron, glial cell) or subcellular organelle (e.g., mitochondria). Determining the site of action and precise mechanisms triggered by cannabinoid receptor activation at a local cellular and subcellular level helps us understand hippocampal pathophysiological states. In doing so, past and current research have advanced our knowledge of cannabinoid functions and proposed novel routes for potential therapeutics. By outlining these data in this work, we aim to showcase current findings and highlight the pathophysiological impact of the cannabinoid receptor type 1 (CB1) localization/activation in hippocampal circuits.This work was supported by Ikerbasque, MINECO (Ministerio de Economia y Competitividad) PGC2018-093990-A-I00 (MICIU/AEI/FEDER, UE), and Endeavour Scholarship Scheme (Malta-EU) (to E.S.-G.); Basque Government (IT1230-19), Red de Trastornos Adictivos, Instituto de Salud Carlos III (ISC-III) and European Regional Development Funds-European Union (ERDF-EU; RD16/0017/0012), Ministry of Science and Innovation (PID2019-107548RB-I00) (to P.G.)

Omega-3 gantz-azidoen propietate onuragarriak zenbait egoera klinikotan

Omega-3 fatty acids (FA) are essential long-chain polyunsaturated FA, amongst others, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The main food source of omega-3 is the oily fish which is found in salmon, anchovy or tuna. A diet enriched with omega-3 is known to favour healthy states by promoting molecular and functional changes during brain damage recovery, membranes fluidity, energy metabolism regulation, release of signalling molecules or gene expression. Likewise, the activation of signalling pathways by omega-3 improves neural transmission and plasticity and decreases oxidative stress and inflammation in cells, particularly in neurons. Therefore, omega-3 supplements have been used to prevent or treat many human disorders. This review is intended to provide the stateof- the art of omega-3 as a natural component with beneficial therapeutic properties in cardiovascular and neurodegenerative diseases (Alzheimer and Parkinson), cancer, alcoholism and overweight. Lastly, some insights into the potential benefits of omega-3 supplementation to dodge or treat some other diseases in the future are also considered.; Kate luzeko omega-3 mantenugaiak, azido α-linolenikoa (ALA), azido eikosapentaenoikoa (EPA) eta azido dokosahexaenoikoa (DHA), dietaren bitartez bereganatzen diren gantz-azido (GA) poliasegabeak dira. Propietate antioxidatzaileak barne hartzen dituzten hiru osagai horien elikagai-iturri nagusia arrain koipetsua (izokina, antxoa, hegalaburra…) eta horretatik eratorritako arrain-olioa dira batez ere. Omega-3 GA osagarriaz aberastutako dietak aldaketa molekular zein funtzional mesedegarriak eragiten ditu garunaren garapen prozesuan, zenbait garun lesioren berreskurapenean parte hartzen. Gehigarri horrek mintz zelularraren fluidotasuna areagotzen du, eta metabolismoaren erregulazioan parte hartzen du, seinaleztapen molekulen askapena sustatuz eta gene espresioan eraginez. Bi ekintza horien bidez seinaleztapen bideak aktibatzen dira, eta ondorioz garun plastikotasuna eta transmisio sinaptikoa suspertu. Areago, omega-3 GAk zeluletan oro har, eta neuronetan bereziki, oxidazio-estresak eta hanturak eragindako kalteak murriztu ditzake. Horregatik guztiagatik, omega-3 osagarria hainbat patologietan prebentzioan edo tratamenduan erabili da. Berrikuspen honek laburbiltzen ditu kate luzeko omega-3 GAetan aberastutako tratamenduak bihotz hodietako gaixotasunetan, minbizian, neuroendekapenezko gaixotasunetan (Alzheimer eta Parkinson), alkoholismoan eta gainpisuan, oinarrizko ikerkuntzan eta ikerketa klinikoan frogatu eta egiaztatu diren aurrerapen terapeutiko berriak; eta etorkizunera begira beste hainbat gaixotasuni aurrea hartzeko edo haiek tratatzeko potentzialtasun handiko eta albo ondoriorik gabeko osagarri ez-inbaditzaile aproposa izan daitekeela iradokitzen du

Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle

Funding: This work was supported by CIBERobn (CB06/03/1008), Ministerio de Economía y Competitividad (MINECO) (PG: BFU2012-33334), Instituto de Salud Carlos III (ISCIII), MINECO, co-funded by UE-ERDF program (JS: CP12/03109), Red de Trastornos Adictivos (FRF: RD12/0028/0001, PG: RD12/0028/0004, JM: RD12/0028/0013), The Basque Country Government (PG: BCG IT764-13), Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE-ERDF (FRF: CTS-8221, JM: CVI-6656), Consejería de Salud, Junta de Andalucía, UE-ERDF (FRF: SAS111224), and University of the Basque Country UPV/EHU (PG: UFI11/41). JS, FJP and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII, UE-ERDF (CP12/03109, CP14/00212, and CP14/00173 respectively)Peer reviewedPublisher PD

Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence

Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, and the endocannabinoid, 2-arachydonoyl-glycerol (2-AG), rescues synaptic plasticity and memory impaired in adult rodents upon adolescent EtOH intake. However, the mechanisms by which EE improves memory are unknown. We investigated this in adolescent male C57BL/6J mice exposed to a drinking in the dark (DID) procedure four days per week for a duration of 4 weeks. After DID, the mice were nurtured under an EE for 2 weeks and were subjected to the Barnes Maze Test performed the last 5 days of withdrawal. The EE rescued memory and restored the EtOH-disrupted endocannabinoid (eCB)-dependent excitatory long-term depression at the dentate medial perforant path synapses (MPP-LTD). This recovery was dependent on both the cannabinoid CB1 receptor and group I metabotropic glutamate receptors (mGluRs) and required 2-AG. Also, the EE had a positive effect on mice exposed to water through the transient receptor potential vanilloid 1 (TRPV1) and anandamide (AEA)-dependent MPP long-term potentiation (MPP-LTP). Taken together, EE positively impacts different forms of excitatory synaptic plasticity in water- and EtOH-exposed brains.This research was funded by ISCIII (“RD16/0017/0012” to P.G.), co-funded by ERDF/ESF, “Investing in your future”; The Basque Government (IT1230-19 to P.G.); Ministry of Science and Innovation (PID2019-107548RB-I00 to P.G.); Ph.D. contract from MINECO (BES-2013-065057 to S.P.); Ph.D. contract from UPV/EHU (PIF 18/315 to L.L.), and Ph.D. contract from UPV/EHU (PIF 19/164 to M.S.)

GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus

Background: Type-1 cannabinoid receptors (CB1R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. Methodology/Principal Findings: Light and electron microscopy techniques were used to analyze CB1R distribution in the VMH of CB1R-WT, CB1R-KO and conditional mutant mice bearing a selective deletion of CB1R in cortical glutamatergic (Glu-CB1R-KO) or GABAergic neurons (GABA-CB1R-KO). At light microscopy, CB1R immunolabeling was observed in the VMH of CB1R-WT and Glu-CB1R-KO animals, being remarkably reduced in GABA-CB1R-KO mice. In the electron microscope, CB1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB1R immunopositive profiles and CB1R density in terminals making asymmetric or symmetric synapses in CB1R-WT mice. Furthermore, the proportion of CB1R immunopositive terminals/preterminals in CB1R-WT and Glu-CB1R-KO mice was reduced in GABA-CB1R-KO mutants. CB1R density was similar in all animal conditions. Finally, the percentage of CB1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB1R-KO mutants relative to CB1R-WT mice, indicating that CB1R was distributed in cortical and subcortical excitatory synaptic terminals. Conclusions/Significance: Our anatomical results support the idea that the VMH is a relevant hub candidate in the endocannabinoid-mediated modulation of the excitatory and inhibitory neurotransmission of cortical and subcortical pathways regulating essential hypothalamic functions for the individual's survival such as the feeding behavior.L. Reguero is in receipt of a Predoctoral Fellowship from the Basque Country Government (BFI 07.286); I. Buceta is in receipt of a Predoctoral Fellowship from the Basque Country University. Dr. Pedro Grandes' laboratory is supported by The Basque Country Government grant GIC07/70-IT-432-07, by Ministerio de Ciencia e Innovacion (SAF2009-07065) and by Red de Trastornos Adictivos, RETICS, Instituto de Salud Carlos III, MICINN, grant RD07/0001/2001. Dr. Giovanni Marsicano's laboratory is supported by AVENIR/INSERM (with the Fondation Bettencourt-Schueller), by ANR (ANR-06-NEURO-043-01), by European Foundation for the Study of Diabetes (EFSD), by the EU-FP7 (REPROBESITY, contract number HEALTH-F2-2008-223713) and European Commission Coordination Action ENINET (contract number LSHM-CT-2005-19063). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Emerging trends in reassessing translation, conflict, and memory

New Approaches on Translation, Conflict, and Memory: Narratives of the Spanish Civil War and the Dictatorship is a collection of essays that endeavours to establish a new dialogue between translation, conflict, and memory studies. Focusing on cultural representations of the Spanish Civil War and the Franco Dictatorship, it explores the significance and the effect of translation within Spain and beyond. Drawing on fictional and non-fictional texts, reports from war zones, and audiovisual productions, the contributors to this volume examine the scope of translation in transmitting the conflict and the dictatorship from a contemporary perspective. Narratives produced during and after the Civil War and the dictatorship both in Spain and abroad have led to new debates arising from the reassessment of a conflict that continues to resonate

[Mucho más guapo que Clark (Málaga.2002)]

Ángel González: tiempo insegur