CRIS

Permanent URI for this communityhttps://investigadores.udd.cl/handle/123456789/1

Browse

Settings

Subject: search.filters.subject.alcoholism

Search Results

Now showing 1 - 10 of 15
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes
    (2024)
    Gonzalo I. Gómez
    ;
    Claudia García-Rodríguez
    ;
    Jesús E. Marillán
    ;
    Sergio A. Vergara
    ;
    Tanhia F. Alvear
    <jats:p>Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca<jats:sup>2+</jats:sup> and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca<jats:sup>2+</jats:sup> overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca<jats:sup>2+</jats:sup> signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> linked to extracellular Ca<jats:sup>2+</jats:sup> influx and IP<jats:sub>3</jats:sub>-evoked Ca<jats:sup>2+</jats:sup> release from intracellular Ca<jats:sup>2+</jats:sup> stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>. The [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.</jats:p>
      11Scopus© Citations 4
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 2  2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use
    (2023)
    María Elena Quintanilla
    ;
    Paola Morales
    ;
    Daniela Santapau
    ;
    Alba Ávila
    ;
    Carolina Ponce
    <jats:p>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.</jats:p>
      7Scopus© Citations 9
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Innate gut microbiota predisposes to high alcohol consumption
    (2021)
    EZQUER, EDUARDO FERNANDO  
    ;
    Maria Elena Quintanilla
    ;
    Francisco Moya‐Flores
    ;
    Paola Morales
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    Scopus© Citations 34  5
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 34  2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 22  2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Childhood adversity increases risk of psychotic experiences in patients with substance use disorder
    (2022)
    Ignacio Bórquez-Infante
    ;
    Javiera Vasquez
    ;
    Sofía Dupré
    ;
    Eduardo A. Undurraga
    ;
    Nicolás A. Crossley
      4Scopus© Citations 10
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    GERO Cohort Protocol, Chile, 2017–2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly
    (2020)
    Andrea Slachevsky  
    ;
    Pedro Zitko
    ;
    David Martínez-Pernía
    ;
    Gonzalo Forno
    ;
    Felipe A. Court
    <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The GERO cohort aims the recruitment of 300 elderly subjects (&gt; 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research.</jats:p></jats:sec><jats:sec><jats:title>Trial registration</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04265482">NCT04265482</jats:ext-link>in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.</jats:p></jats:sec>
    Scopus© Citations 13  2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 21  1
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 4  3