Browsing by Author "Cerpa Nebott, Waldo"

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    Episodic Binge-like Ethanol Reduces Skeletal Muscle Strength Associated with Atrophy, Fibrosis, and Inflammation in Young Rats
    (2023) Cáceres-Ayala, Constanza; Mira, Rodrigo G.; Acuña, María José; Brandan, Enrique; Cerpa Nebott, Waldo; Rebolledo, Daniela L.
    Binge Drinking (BD) corresponds to episodes of ingestion of large amounts of ethanol in a short time, typically ≤2 h. BD occurs across all populations, but young and sports-related people are especially vulnerable. However, the short- and long-term effects of episodic BD on skeletal muscle function have been poorly explored. Young rats were randomized into two groups: control and episodic Binge-Like ethanol protocol (BEP) (ethanol 3 g/kg IP, 4 episodes of 2-days ON-2-days OFF paradigm). Muscle function was evaluated two weeks after the last BEP episode. We found that rats exposed to BEP presented decreased muscle strength and increased fatigability, compared with control animals. Furthermore, we observed that skeletal muscle from rats exposed to BEP presented muscle atrophy, evidenced by reduced fiber size and increased expression of atrophic genes. We also observed that BEP induced fibrotic and inflammation markers, accompanied by mislocalization of nNOSµ and high levels of protein nitration. Our findings suggest that episodic binge-like ethanol exposure alters contractile capacity and increases fatigue by mechanisms involving atrophy, fibrosis, and inflammation, which remain for at least two weeks after ethanol clearance. These pathological features are common to several neuromuscular diseases and might affect muscle performance and health in the long term.
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    How Are Synapses Born? A Functional and Molecular View of the Role of the Wnt Signaling Pathway
    (2022) Bonansco, Christian; Cerpa Nebott, Waldo; Inestrosa, Nibaldo C.
    Synaptic transmission is a dynamic process that requires precise regulation. Early in life, we must be able to forge appropriate connections (add and remove) to control our behavior. Neurons must recognize appropriate targets, and external soluble factors that activate specific signaling cascades provide the regulation needed to achieve this goal. Wnt signaling has been implicated in several forms of synaptic plasticity, including functional and structural changes associated with brain development. The analysis of synapses from an electrophysiological perspective allows us to characterize the functional role of cellular signaling pathways involved in brain development. The application of quantal theory to principles of developmental plasticity offers the possibility of dissecting the function of structural changes associated with the birth of new synapses as well as the maturation of immature silent synapses. Here, we focus on electrophysiological and molecular evidence that the Wnt signaling pathway regulates glutamatergic synaptic transmission, specifically N-methyl-d-aspartate receptors (NMDARs), to control the birth of new synapses. We also focus on the role of Wnts in the conversion of silent synapses into functional synapses.
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    The functional and molecular effects of problematic alcohol consumption on skeletal muscle: a focus on athletic performance
    (2022) Caceres-Ayala, Constanza; Pautassi, Ricardo M.; Acuña, María José; Cerpa Nebott, Waldo; Rebolledo, Daniela L.
    Background: Chronic alcohol misuse is associated with alcoholic myopathy, characterized by skeletal muscle weakness and atrophy. Moreover, there is evidence that sports-related people seem to exhibit a greater prevalence of problematic alcohol consumption, especially binge drinking (BD), which might not cause alcoholic myopathy but can negatively impact muscle function and amateur and professional athletic performance. Objective: To review the literature concerning the effects of alcohol consumption on skeletal muscle function and structure that can affect muscle performance. Methodology: We examined the currently available literature (PubMed, Google Scholars) to develop a narrative review summarizing the knowledge about the effects of alcohol on skeletal muscle function and exercise performance, obtained from studies in human beings and animal models for problematic alcohol consumption. Results: Exercise- and sport-based studies indicate that alcohol consumption can negatively affect muscle recovery after vigorous exercise, especially in men, while women seem less affected. Clinical studies and pre-clinical laboratory research have led to the knowledge of some of the mechanisms involved in alcohol-related muscle dysfunction, including an imbalance between anabolic and catabolic pathways, reduced regeneration, increased inflammation and fibrosis, and deficiencies in energetic balance and mitochondrial function. These pathological features can appear not only under chronic alcohol misuse but also in other alcohol consumption patterns. Conclusions: Most laboratory-based studies use chronic or acute alcohol exposure, while episodic BD, the most common drinking pattern in amateur and professional athletes, is underrepresented. Nevertheless, alcohol consumption negatively affects skeletal muscle health through different mechanisms, which collectively might contribute to reduced sports performance.
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    The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release
    (2024) Duarte, Y.; Quintana-Donoso, D.; Moraga-Amaro, R.; Dinamarca, I.; Lemunao, Y.; Cardenas, K.; Bahamonde, T.; Barrientos, T.; Olivares, P.; Navas, C.; Carvajal, F.J.; Santibanez, Y.; Castro-Lazo, R.; Paz Meza, M.; Jorquera, R.; Gomez, G.I.; Henke, M.; Alarcon, R.; Gabriel, L.A.; Schiffmann, S.; Cerpa Nebott, Waldo; Retamal, M.A.; Simon, F.; Linsambarth, S.; Gonzalez-Nilo, F.; Stehberg, J.
    The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.