Browsing by Author "Berrios, Pablo"

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    Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use
    (2023) Ezquer, Fernando; Ezquer, Marcelo; Gallardo, Javiera; Quintanilla, María; Morales, Paola; Santapau, Daniela; Ávila, Alba; Ponce, Carolina; Berrios, Pablo; Olivares, Belén; Herrera, Mario; Israel, Yedy
    Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal-striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.
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    Cuantificación de miARNs antiinflamatorios en microglias y astrocitos purificados y su contraste con el estado hepático en ratones que consumieron alcohol de forma voluntaria y crónica
    (2023) Herreros, Belén; Sepúlveda, Luis; Montenegro, Ignacio; Carine, Jesusariki; Berrios, Pablo
    El alcohol es una sustancia psicoactiva que afecta al hígado y al cerebro. El alcohol se metaboliza en sustancias tóxicas y radicales libres que dañan los tejidos hepáticos y pueden causar hepatitis alcohólica y cirrosis hepática. El alcohol también produce inflamación en el cerebro, que implica la activación de las células gliales y la liberación de sustancias que causan daño cerebral. Los microRNA son moléculas pequeñas que regulan la expresión génica y pueden tener efectos antiinflamatorios o proinflamatorios. Objetivo: En este estudio se midieron los niveles de varios microRNA en ratones que consumían o no alcohol, y se confirmó el consumo de alcohol y el daño hepático con pruebas de sangre y tejido. Metodología: Se extrajo parte del estriado e hipocampo de cada ratón, y en ambas áreas se purificaron astrocitos y microglías. La medición de los niveles de miRNAs se realizó a través de qPCR. Resultado: Desafortunadamente, no se encontraron diferencias significativas.
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    Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice
    (2022) Charkoftaki, Georgia; Tan, Wan Ying; Berrios, Pablo; Orlicky, David; Prakash, Jaya; Garcia, Rolando; Aalizadeh, Reza; Thomaidis, Nikolaos; Thompson, David; Vasiliou, Vasilis
    Alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. The liver sustains the earliest and the greatest degree of tissue injury due to chronic alcohol consumption and it has been estimated that alcoholic liver disease (ALD) accounts for almost 50% of all deaths from cirrhosis in the world. In this study, we used a modified Lieber-DeCarli (LD) diet to treat mice with alcohol and simulate chronic alcohol drinking. Using an untargeted metabolomics approach, our aim was to identify the various metabolites and pathways that are altered in the early stages of ALD. Histopathology showed minimal changes in the liver after 6 weeks of alcohol consumption. However, untargeted metabolomics analyses identified 304 metabolic features that were either up- or down-regulated in the livers of ethanol-consuming mice. Pathway analysis revealed significant alcohol-induced alterations, the most significant of which was in the FXR/RXR activation pathway. Targeted metabolomics focusing on bile acid biosynthesis showed elevated taurine-conjugated cholic acid compounds in ethanol-consuming mice. In summary, we showed that the changes in the liver metabolome manifest very early in the development of ALD, and when minimal changes in liver histopathology have occurred. Although alterations in biochemical pathways indicate a complex pathology in the very early stages of alcohol consumption, bile acid changes may serve as biomarkers of the early onset of ALD.

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