Browsing by Author "Martinez, Pablo"

Now showing 1 - 7 of 7
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    Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala
    (2022) Linsambarth, Sergio; Carvajal Cachaña, Francisco Javier; Moraga Amaro, Rodrigo; Mendez, Luis; Tamburini, Giovanni; Jimenez, Ivanka; Antonio Verdugo, Daniel; Gomez, Gonzalo, I; Jury, Nur; Martinez, Pablo; van Zundert, Brigitte; Varela Nallar, Lorena; Retamal, Mauricio A.; Martin, Claire; Altenberg, Guillermo A.; Fiori, Mariana C.; Cerpa Nebott, Waldo Francisco; Orellana Roca, Juan Andrés; Stehberg, Jimmy
    Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the gliotransmitters released, and their mechanisms of action remain elusive. Here, we report that fear conditioning training elevated Cx43 hemichannel activity in astrocytes from the basolateral amygdala (BLA). The selective blockade of Cx43 hemichannels by microinfusion of TAT-Cx43L2 peptide into the BLA induced memory deficits 1 and 24 h after training, without affecting learning. The memory impairments were prevented by the co-injection of glutamate and D-serine, but not by the injection of either alone, suggesting a role for NMDA receptors (NMDAR). The incubation with TAT-Cx43L2 decreased NMDAR-mediated currents in BLA slices, effect that was also prevented by the addition of glutamate and D-serine. NMDARs in primary neuronal cultures were unaffected by TAT-Cx43L2, ruling out direct effects of the peptide on NMDARs. Finally, we show that D-serine permeates through purified Cx43 hemichannels reconstituted in liposomes. We propose that the release of glutamate and D-serine from astrocytes through Cx43 hemichannels is necessary for the activation of post-synaptic NMDARs during training, to allow for the formation of short-term and subsequent long-term memory, but not for learning per se.
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    Delphi-validation of a Psychotherapeutic Competencies Training Protocol (PCTP) for the treatment of depression in primary care: evidence-based practice and practice-based evidence (Validación Delphi de un Protocolo de Entrenamiento en Competencias Psicoterapéuticas (PECP) para el tratamiento de la depresión en atención primaria: práctica basada en la evidencia y evidencia basada en la práctica)
    (Taylor and Francis Ltd., 2022) Parra Cieciwa, Guillermo de la; Crempien Robles, Carla Erika Federica; Morales Silva, Susana; Errazuriz Concha, Antonia; Martinez, Pablo; Aravena, Catalina; Zuñiga Caiseo, Ana Karina; Ferrari, T.eresa
    Following the guidelines of practice-oriented research (POR), a Psychotherapeutic Competencies Training Protocol (PCTP-1) for treating depression in primary health care (PHC) was developed and validated by a group of clinician-researchers, grounded on evidence-based practice and practice-based evidence. This protocol was subjected to a Delphi validation by a panel of judges, including clinicians, researchers and public health experts. After three rounds, a consensus of 85% in all PCTP-1 modules was achieved, resulting in version 2 of the protocol (PCTP-2), which will be used to develop a Psychotherapeutic Competencies Training Online Programme (PColP) for the treatment of depression in PHC. The basic principles of the protocol and its validation process are described and discussed, underscoring its contribution to clinicians who must face the challenges of treating patients with depression in PHC.
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    Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons
    (2022) Arredondo, Cristian; Cefaliello, Carolina; Dyrda, Agnieszka; Jury, Nur; Martinez, Pablo; Diaz, Ivan; Amaro, Armando; Tran, Helene; Morales, Danna; Pertusa, Maria; Stoica, Lorelei; Fritz, Elsa; Corvalan, Daniela; Abarzua, Sebastian; Mendez-Ruette, Maxs; Fernandez, Paola; Rojas, Fabiola; Kumar, Meenakshi Sundaram; Aguilar, Rodrigo; Almeida, Sandra; Weiss, Alexandra; Bustos, Fernando J.; Gonzalez-Nilo, Fernando; Otero, Carolina; Tevy, Maria Florencia; Bosco, Daryl A.; Saez, Juan C.; Kahne, Thilo; Gao, Fen-Biao; Berry, James D.; Nicholson, Katharine; Sena-Esteves, Miguel; Madrid, Rodolfo; Varela, Diego; Montecino, Martin; Brown, Robert H.; van Zundert, Brigitte
    Non-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/ FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD.
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    Population-attributable risk of adverse childhood experiences for high suicide risk, psychiatric admissions, and recurrent depression, in depressed outpatients
    (2021) Gloger, Sergio; Martinez, Pablo; Behn, Alex; Victoria Chacon, M.; Cottin, Marianne; Diez de Medina, Dante; Vohringer, Paul A.
    Background: Population-attributable risk (PAR) may help estimate the potential contribution of adverse childhood experiences (ACEs) to serious clinical presentations of depression, characterized by suicidality, previous psychiatric admissions, and episode recurrence.
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    Predictors of Survival Outcomes in Non-Metastatic Renal Cell Carcinoma in Latin America and Spain: A Multicentric Analysis
    (2019) Zequi, Stenio de Cassio; Mourao, Thiago Camelo; de Oliveira, Max Moura; Curado, Maria Paula; Gueglio, Guilhermo; da Costa, Walter Henriques; Zuniga, Alvaro; Bengio, Ruben; Scorticati, Carlos; Rodriguez, Francisco; Autran, Ana Maria; Martinez, Pablo; Ameri, Carlos; Mingote, Pablo; Secin, Fernando Pablo; Decia, Ricardo; da Cunha, Isabela Werneck; Guimaraes, Gustavo Cardoso; Glina, Sidney; Palou, Joan; Abreu, Diego
    Background: Renal cell carcinoma (RCC) is a lethal neoplasia. Data from Latin America are scarce, and the distinct ethnic origins of this population could affect predictive or prognostic factors.
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    Technology-Assisted Collaborative Care Program for People with Diabetes and/or High Blood Pressure Attending Primary Health Care: A Feasibility Study
    (2021) Martinez, Pablo; Guajardo, Viviana; Gomez, Victor E.; Brandt, Sebastian; Szabo, Wilsa; Soto-Brandt, Gonzalo; Farhang, Maryam; Baeza, Paulina; Campos, Solange; Herrera, Pablo; Rojas, Graciela
    The comorbidity of depression with physical chronic diseases is usually not considered in clinical guidelines. This study evaluated the feasibility of a technology-assisted collaborative care (TCC) program for depression in people with diabetes and/or high blood pressure (DM/HBP) attending a primary health care (PHC) facility in Santiago, Chile. Twenty people diagnosed with DM/HBP having a Patient Health Questionnaire-9 score & GE; 15 points were recruited. The TCC program consisted of a face-to-face, computer-assisted psychosocial intervention (CPI, five biweekly sessions), telephone monitoring (TM), and a mobile phone application for behavioral activation (CONEMO). Assessments of depressive symptoms and other health-related outcomes were made. Thirteen patients completed the CAPI, 12 received TM, and none tried CONEMO. The TCC program was potentially efficacious in treating depression, with two-thirds of participants achieving response to depression treatment 12 weeks after baseline. Decreases were observed in depressive symptoms and healthcare visits and increases in mental health-related quality of life and adherence to treatment. Patients perceived the CPI as acceptable. The TCC program was partially feasible and potentially efficacious for managing depression in people with DM/HBP. These data are valuable inputs for a future randomized clinical trial.
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    The contribution of early adverse stress to complex and severe depression in depressed outpatients
    (2021) Gloger, Sergio; Vohringer, Paul A.; Martinez, Pablo; Victoria Chacon, M.; Caceres, Cristian; Diez de Medina, Dante; Cottin, Marianne; Behn, Alex
    Background To assess whether linear effects or threshold effects best describe the association between early adverse stress (EAS) and complex and severe depression (i.e., depression with treatment resistance, psychotic symptoms, and/or suicidal ideation), and to examine the attributable risk of complex and severe depression associated with EAS.