DSpace Angular :: Browsing by Author "Quintanilla, Rodrigo A."

Browsing by Author "Quintanilla, Rodrigo A."

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Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment
(2018) Tapia-Rojas, Cheril; Carvajal Cachaña, Francisco Javier; Mira, Rodrigo G.; Arce, Camila; Manuel Lerma-Cabrera, Jose; Orellana Roca, Juan Andrés; Cerpa Nebott, Waldo Francisco; Quintanilla, Rodrigo A.
Alcohol consumption during adolescence alters the hippocampal response to traumatic brain injury
(2020) Mira, Rodrigo G.; Lira, Matías; Quintanilla, Rodrigo A.; Cerpa Nebott, Waldo Francisco
Binge drinking is the consumption of large volumes of alcohol in short periods and exerts its effects on the central nervous system, including the hippocampus. We have previously shown that binge drinking alters mitochondrial dynamics and induces neuroinflammation in the hippocampus of adolescent rats. Mild traumatic brain injury (mTBI), is regularly linked to alcohol consumption and share mechanisms of brain damage. In this context, we hypothesized that adolescent binge drinking could prime the development of brain damage generated by mTBI. We found that alcohol binge drinking induced by the “drinking in the dark” (DID) paradigm increases oxidative damage and astrocyte activation in the hippocampus of adolescent mice. Interestingly, adolescent animals submitted to DID showed decreased levels of mitofusin 2 that controls mitochondrial dynamics. When mTBI was evaluated as a second challenge, hippocampi from animals previously submitted to DID showed a reduction in dendritic spine number and a different spine profile. Mitochondrial performance could be compromised by alterations in mitochondrial fission in DID-mTBI animals. These data suggest that adolescent alcohol consumption can modify the progression of mTBI pathophysiology. We propose that mitochondrial impairment and oxidative damage could act as priming factors, modifying predisposition against mTBI effects.
Alcohol impairshippocampal function:FromNMDAreceptorsynaptic transmissiontomitochondrial function
(2019) Mira, Rodrigo G.; Tapia Rojas, Cheril; Pérez, María José; Jara, Claudia; Vergara, Erick H.; Quintanilla, Rodrigo A.; Cerpa Nebott, Waldo Francisco
Many studies have reported that alcohol produces harmful effects on several brain structures, including the hippocampus, in both rodents and humans. The hippocampus is one of the most studied areas of the brain due to its function in learning and memory, and a lot of evidence suggests that hippocampal failure is responsible for the cognitive loss present in individuals with recurrent alcohol consumption. Mitochondria are organelles that generate the energy needed for the brain to maintain neuronal communication, and their functional failure is considered a mediator of the synaptic dysfunction induced by alcohol. In this review, we discuss the mechanisms of how alcohol exposure affects neuronal communication through the impairment of glutamate receptor (NMDAR) activity, neuroinflammatory events and oxidative damage observed after alcohol exposure, all processes under the umbrella of mitochondrial function. Finally, we discuss the direct role of mitochondrial dysfunction mediating cognitive and memory decline produced by alcohol exposure and their consequences associated with neurodegeneration.
Carbamylated form of human erythropoietin normalizes cardiorespiratory disorders triggered by intermittent hypoxia mimicking sleep apnea syndrome
(LIPPINCOTT WILLIAMS & WILKINS, 2021) Andrade, David C.; Toledo, Camilo; Diaz, Hugo S.; Pereyra, Katherin, V; Schwarz, Karla G.; Diaz Jara, Esteban; Melipillan, Claudia; Rios Gallardo, Angelica P.; Uribe Ojeda, Atenea; Alcayaga, Julio; Quintanilla, Rodrigo A.; Iturriaga, Rodrigo; Richalet, Jean Paul; Voituron, Nicolas; Del Rio, Rodrigo
Background and objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuroprotective profile without increasing red blood cells number. However, no studies have evaluated the potential therapeutic effect of cEpo on CIH-related cardiorespiratory disorders. We aimed to determine whether cEpo normalized the CIH-enhanced carotid body ventilatory chemoreflex, the hypertension and ventilatory disorders in rats. Methods: Male Sprague-Dawley rats (250 g) were exposed to CIH (5% O-2, 12/h, 8 h/day) for 28 days. cEPO (20 mu g/kg, i.p) was administrated from day 21 every other day for one more week. Cardiovascular and respiratory function were assessed in freely moving animals. Results: Twenty-one days of CIH increased carotid body-mediated chemoreflex responses as evidenced by a significant increase in the hypoxic ventilatory response (FiO2 10%) and triggered irregular eupneic breathing, active expiration, and produced hypertension. cEpo treatment significantly reduced the carotid body--chemoreflex responses, normalizes breathing patterns and the hypertension in CIH. In addition, cEpo treatment effectively normalized carotid body chemosensory responses evoked by acute hypoxic stimulation in CIH rats. Conclusion: Present results strongly support beneficial cardiorespiratory therapeutic effects of cEpo during CIH exposure.
Effect of Alcohol on Hippocampal-Dependent Plasticity and Behavior: Role of Glutamatergic Synaptic Transmission
(Frontiers Media S.A., 2020) Mira, Rodrigo G.; Lira, Matias; Cerpa Nebott Waldo Francisco; Tapia-Rojas, Cheril; Rebolledo, Daniela; Quintanilla, Rodrigo A.
© Copyright © 2020 Mira, Lira, Tapia-Rojas, Rebolledo, Quintanilla and Cerpa. Problematic alcohol drinking and alcohol dependence are an increasing health problem worldwide. Alcohol abuse is responsible for approximately 5% of the total deaths in the world, but addictive consumption of it has a substantial impact on neurological and memory disabilities throughout the population. One of the better-studied brain areas involved in cognitive functions is the hippocampus, which is also an essential brain region targeted by ethanol. Accumulated evidence in several rodent models has shown that ethanol treatment produces cognitive impairment in hippocampal-dependent tasks. These adverse effects may be related to the fact that ethanol impairs the cellular and synaptic plasticity mechanisms, including adverse changes in neuronal morphology, spine architecture, neuronal communication, and finally an increase in neuronal death. There is evidence that the damage that occurs in the different brain structures is varied according to the stage of development during which the subjects are exposed to ethanol, and even much earlier exposure to it would cause damage in the adult stage. Studies on the cellular and cognitive deficiencies produced by alcohol in the brain are needed in order to search for new strategies to reduce alcohol neuronal toxicity and to understand its consequences on memory and cognitive performance with emphasis on the crucial stages of development, including prenatal events to adulthood.
Genetic ablation of tau improves mitochondrial function and cognitive abilities in the hippocampus
(2018) Jara, Claudia; Aránguiz, Alejandra; Cerpa Nebott, Waldo Francisco; Tapia-Rojas, Cheril; Quintanilla, Rodrigo A.
Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats : Effects on Neuroinflammation and Astrocyte Arborization
(2018) Gomez, Gonzalo I.; Falcon, Romina V.; Maturana, Carola J.; Labra, Valeria C.; Salgado Cortés, Nicole Andrea; Rojas Vidal, Consuelo Antonia; Oyarzun, Juan E.; Cerpa Nebott, Waldo Francisco; Quintanilla, Rodrigo A.; Orellana Roca, Juan Andrés
Mild Traumatic Brain Injury Induces Mitochondrial Calcium Overload and Triggers the Upregulation of NCLX in the Hippocampus
(2023) Mira, Rodrigo G.; Quintanilla, Rodrigo A.; Cerpa Nebott, Waldo Francisco
Traumatic brain injury (TBI) is brain damage due to external forces. Mild TBI (mTBI) is the most common form of TBI, and repeated mTBI is a risk factor for developing neurodegenerative diseases. Several mechanisms of neuronal damage have been described in the cortex and hippocampus, including mitochondrial dysfunction. However, up until now, there have been no studies evaluating mitochondrial calcium dynamics. Here, we evaluated mitochondrial calcium dynamics in an mTBI model in mice using isolated hippocampal mitochondria for biochemical studies. We observed that 24 h after mTBI, there is a decrease in mitochondrial membrane potential and an increase in basal matrix calcium levels. These findings are accompanied by increased mitochondrial calcium efflux and no changes in mitochondrial calcium uptake. We also observed an increase in NCLX protein levels and calcium retention capacity. Our results suggest that under mTBI, the hippocampal cells respond by incrementing NCLX levels to restore mitochondrial function.
Mitochondrial permeability transition pore induces mitochondria injury in Huntington disease
(2013) Quintanilla, Rodrigo A.; Jin, Youngnam N.; Bernhardi Montgomery, Rommy von; Johnson, Gail V.
Abstract Background Mitochondrial impairment has been implicated in the pathogenesis of Huntington’s disease (HD). However, how mutant huntingtin impairs mitochondrial function and thus contributes to HD has not been fully elucidated. In this study, we used striatal cells expressing wild type (STHdhQ7/Q7) or mutant (STHdhQ111/Q111) huntingtin protein, and cortical neurons expressing the exon 1 of the huntingtin protein with physiological or pathological polyglutamine domains, to examine the interrelationship among specific mitochondrial functions. Results Depolarization induced by KCl resulted in similar changes in calcium levels without compromising mitochondrial function, both in wild type and mutant cells. However, treatment of mutant cells with thapsigargin (a SERCA antagonist that raises cytosolic calcium levels), resulted in a pronounced decrease in mitochondrial calcium uptake, increased production of reactive oxygen species (ROS), mitochondrial depolarization and fragmentation, and cell viability loss. The mitochondrial dysfunction in mutant cells was also observed in cortical neurons expressing exon 1 of the huntingtin protein with 104 Gln residues (Q104-GFP) when they were exposed to calcium stress. In addition, calcium overload induced opening of the mitochondrial permeability transition pore (mPTP) in mutant striatal cells. The mitochondrial impairment observed in mutant cells and cortical neurons expressing Q104-GFP was prevented by pre-treatment with cyclosporine A (CsA) but not by FK506 (an inhibitor of calcineurin), indicating a potential role for mPTP opening in the mitochondrial dysfunction induced by calcium stress in mutant huntingtin cells. Conclusions Expression of mutant huntingtin alters mitochondrial and cell viability through mPTP opening in striatal cells and cortical neurons.
Neurodegeneration in Multiple Sclerosis: The Role of Nrf2-Dependent Pathways
(2022) Maldonado, Paloma P.; Guevara, Coram; Olesen, Margrethe A.; Orellana Roca, Juan Andrés; Quintanilla, Rodrigo A.; Ortiz, Fernando C.
Multiple sclerosis (MS) encompasses a chronic, irreversible, and predominantly immune-mediated disease of the central nervous system that leads to axonal degeneration, neuronal death, and several neurological symptoms. Although various immune therapies have reduced relapse rates and the severity of symptoms in relapsing-remitting MS, there is still no cure for this devastating disease. In this brief review, we discuss the role of mitochondria dysfunction in the progression of MS, focused on the possible role of Nrf2 signaling in orchestrating the impairment of critical cellular and molecular aspects such as reactive oxygen species (ROS) management, under neuroinflammation and neurodegeneration in MS. In this scenario, we propose a new potential downstream signaling of Nrf2 pathway, namely the opening of hemichannels and pannexons. These large-pore channels are known to modulate glial/neuronal function and ROS production as they are permeable to extracellular Ca2+ and release potentially harmful transmitters to the synaptic cleft. In this way, the Nrf2 dysfunction impairs not only the bioenergetics and metabolic properties of glial cells but also the proper antioxidant defense and energy supply that they provide to neurons.
Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and A beta Aggregates in Hippocampal Neurons: the Role of Mitochondria
(2017) Godoy, Juan A.; Lindsay, Carolina B.; Quintanilla, Rodrigo A.; Carvajal Cachaña, Francisco Javier; Cerpa Nebott, Waldo Francisco; Inestrosa Cantín, Nibaldo
Revisiting the physiological effects of exercise training on autonomic regulation and chemoreflex control in heart failure : does ejection fraction matter?
(2018) Andrade Andrade, David Cristóbal; Arce Alvarez, Alexis; Toledo, Camilo; Díaz, Hugo S.; Lucero, Claudia; Quintanilla, Rodrigo A.; Schultz, Harold D.; Marcus, Noah J.; Amann, Markus; Del Río, Rodrigo
Understanding Risk Factors for Alzheimer's Disease: Interplay of Neuroinflammation, Connexin-based Communication and Oxidative Stress
(Elsevier Inc., 2012) Quintanilla, Rodrigo A.; Orellana Roca, Juan Andrés; Bernhardi Montgomery, Rommy von
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by dementia and the presence of amyloid plaques and anomalous tau aggregates. Although pathophysiological mechanisms are still unclear, neuroinflammation and glial cell dysfunction have been identified as conspicuous components of AD. Glial cell dysfunction is associated with dysregulated production of inflammation mediators and generation of both reactive oxygen species (ROS) and reactive nitrogen species (RNS), which affect synapses and induce neuronal damage. Importantly, both increased neuroinflammation and ROS/RNS production by glia dysregulate communication mediated by connexin-based channels in brain cells, which could further affect oxidative balance and neuronal viability. Recent evidence suggests that connexin-based channels could be involved in AD pathogenesis. Here we discuss how aging affects neuroinflammation, oxidative stress, and connexin-based channels and the potential relevance of these changes for AD. Understanding how they cooperate as pathogenic mechanisms of AD is promising for the discovery of new therapeutic strategies against neurodegenerative disorders.
Ventilatory and Autonomic Regulation in Sleep Apnea Syndrome: A Potential Protective Role for Erythropoietin?
(2018) Andrade Andrade, David Cristóbal; Haine, Liasmine; Toledo, Camilo; Diaz, Hugo S.; Quintanilla, Rodrigo A.; Marcus, Noah J.; Iturriaga Agüera, Rodrigo; Richalet, Jean-Paul; Voituron, Nicolas; Del Rio, Rodrigo

Browsing by Author "Quintanilla, Rodrigo A."

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