Browsing by Author "Tapia-Rojas, Cheril"

Now showing 1 - 13 of 13
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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.
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    Age-Dependent Behavioral and Synaptic Dysfunction Impairment Are Improved with Long-Term Andrographolide Administration in Long-Lived Female Degus (Octodon degus)
    (2023) Oliva, Carolina A.; Rivera, Daniela S.; Torres, Angie K.; Lindsay, Carolina B.; Tapia-Rojas, Cheril; Bozinovic, Francisco; Inestrosa, Nibaldo C.
    In Octodon degus, the aging process is not equivalent between sexes and worsens for females. To determine the beginning of detrimental features in females and the ways in which to improve them, we compared adult females (36 months old) and aged females (72 months old) treated with Andrographolide (ANDRO), the primary ingredient in Andrographis paniculata. Our behavioral data demonstrated that age does not affect recognition memory and preference for novel experiences, but ANDRO increases these at both ages. Sociability was also not affected by age; however, social recognition and long-term memory were lower in the aged females than adults but were restored with ANDRO. The synaptic physiology data from brain slices showed that adults have more basal synaptic efficiency than aged degus; however, ANDRO reduced basal activity in adults, while it increased long-term potentiation (LTP). Instead, ANDRO increased the basal synaptic activity and LTP in aged females. Age-dependent changes were also observed in synaptic proteins, where aged females have higher synaptotagmin (SYT) and lower postsynaptic density protein-95 (PSD95) levels than adults. ANDRO increased the N-methyl D-aspartate receptor subtype 2B (NR2B) at both ages and the PSD95 and Homer1 only in the aged. Thus, females exposed to long-term ANDRO administration show improved complex behaviors related to age-detrimental effects, modulating mechanisms of synaptic transmission, and proteins.
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    Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
    (2014) Serrano, F. G.; Tapia-Rojas, Cheril; Carvajal, F. J.; Hancke, J.; Cerpa Nebott, Waldo Francisco; Inestrosa Cantín, Nibaldo
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    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.
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    Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus
    (2020) Chang, Lily Y-L; Ardiles, Alvaro O.; Tapia-Rojas, Cheril; Araya, Joaquin; Inestrosa, Nibaldo C.; Palacios, Adrian G.; Acosta, Monica L.
    Accumulation of amyloid-beta (A beta) peptides is regarded as the hallmark of neurodegenerative alterations in the brain of Alzheimer's disease (AD) patients. In the eye, accumulation of A beta peptides has also been suggested to be a trigger of retinal neurodegenerative mechanisms. Some pathological aspects associated with A beta levels in the brain are synaptic dysfunction, neurochemical remodeling and glial activation, but these changes have not been established in the retina of animals with A beta accumulation. We have employed the Octodon degus in which A beta peptides accumulated in the brain and retina as a function of age. This current study investigated microglial morphology, expression of PSD95, synaptophysin, Iba-1 and choline acetyltransferase (ChAT) in the retina of juvenile, young and adult degus using immunolabeling methods. Neurotransmitters glutamate and gamma-aminobutyric acid (GABA) were detected using immunogold labeling and glutamate receptor subunits were quantified using Western blotting. There was an age-related increase in presynaptic and a decrease in post-synaptic retinal proteins in the retinal plexiform layers. Immunolabeling showed changes in microglial morphology characteristic of intermediate stages of activation around the optic nerve head (ONH) and decreasing activation toward the peripheral retina. Neurotransmitter expression pattern changed at juvenile ages but was similar in adults. Collectively, the results suggest that microglial activation, synaptic remodeling and neurotransmitter changes may be consequent to, or parallel to A beta peptide and phosphorylated tau accumulation in the retina.
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    GALECTIN-8 Is a Neuroprotective Factor in the Brain that Can Be Neutralized by Human Autoantibodies
    (2019) Pardo Huguet, Evelyn Cristina; Barake Sabbagh, M. Francisca; Godoy Zeballos, Juan Alejandro; Oyanadel, C.; Espinoza, S.; Metz Baer, Claudia Andrea; Retamal, C.; Massardo Vega, Loreto; Tapia-Rojas, Cheril; Inestrosa Cantín, Nibaldo; Soza, Alejandro; Gonzalez, A.
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    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.
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    How Many Sirtuin Genes Are Out There? Evolution of Sirtuin Genes in Vertebrates With a Description of a New Family Member
    (2023) Opazo, Juan Carlos; Vandewege, Michael W.; Hoffmann, Federico G.; Zavala, Kattina; Melendez, Catalina; Luchsinger, Catalina; Cavieres, Viviana A.; Vargas-Chacoff, Luis; Morera, Francisco J.; Burgos Hitschfeld, Patricia Verónica; Tapia-Rojas, Cheril; Mardones, Gonzalo A.
    Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.
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    Long-term social isolation stress exacerbates sex-specific neurodegeneration markers in a natural model of Alzheimer's disease
    (2023) Oliva, Carolina A.; Lira, Matias; Jara, Claudia; Catenaccio, Alejandra; Mariqueo, Trinidad A.; Lindsay, Carolina B.; Bozinovic, Francisco; Cavieres, Grisel; Inestrosa, Nibaldo C.; Tapia-Rojas, Cheril; Rivera, Daniela S.
    Social interactions have a significant impact on health in humans and animal models. Social isolation initiates a cascade of stress-related physiological disorders and stands as a significant risk factor for a wide spectrum of morbidity and mortality. Indeed, social isolation stress (SIS) is indicative of cognitive decline and risk to neurodegenerative conditions, including Alzheimer's disease (AD). This study aimed to evaluate the impact of chronic, long-term SIS on the propensity to develop hallmarks of AD in young degus (Octodon degus), a long-lived animal model that mimics sporadic AD naturally. We examined inflammatory factors, bioenergetic status, reactive oxygen species (ROS), oxidative stress, antioxidants, abnormal proteins, tau protein, and amyloid-beta (A beta) levels in the hippocampus of female and male degus that were socially isolated from post-natal and post-weaning until adulthood. Additionally, we explored the effect of re-socialization following chronic isolation on these protein profiles. Our results showed that SIS promotes a pro-inflammatory scenario more severe in males, a response that was partially mitigated by a period of re-socialization. In addition, ATP levels, ROS, and markers of oxidative stress are severely affected in female degus, where a period of re-socialization fails to restore them as it does in males. In females, these effects might be linked to antioxidant enzymes like catalase, which experience a decline across all SIS treatments without recovery during re-socialization. Although in males, a previous enzyme in antioxidant pathway diminishes in all treatments, catalase rebounds during re-socialization. Notably, males have less mature neurons after chronic isolation, whereas phosphorylated tau and all detectable forms of A beta increased in both sexes, persisting even post re-socialization. Collectively, these findings suggest that long-term SIS may render males more susceptible to inflammatory states, while females are predisposed to oxidative states. In both scenarios, the accumulation of tau and A beta proteins increase the individual susceptibility to early-onset neurodegenerative conditions such as AD.
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    Non-canonical function of IRE1 alpha determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics
    (2019) Carreras-Sureda, A.; Jana, F.; Urra, H.; Durand, S.; Mortenson, D.E.; Sagredo, A.; Bustos O., Gonzalo; Hazari, Y.; Ramos-Fernandez, E.; Inestrosa Cantín, Nibaldo; Sassano, M.L.; Pihan, P.; Van Vliet, A.R.; Gonzalez-Quiroz, M.; Torres, A.K.; Tapia-Rojas, Cheril; Kerkhofs, M.; Vicente, R.; Kaufman, R.J.; Gonzalez-Billault, C.; Wiseman, R.L.; Agostinis, P.; Bultynck, G.; Court G., Felipe; Kroemer, G.; Cardenas, J.C.; Hetz, C.
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    Tau Deletion Prevents Cognitive Impairment and Mitochondrial Dysfunction Age Associated by a Mechanism Dependent on Cyclophilin-D
    (2021) Jara, Claudia; Cerpa, Waldo; Tapia-Rojas, Cheril; Quintanilla, Rodrigo A.
    Aging is an irreversible process and the primary risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial impairment is a process that generates oxidative damage and ATP deficit; both factors are important in the memory decline showed during normal aging and AD. Tau is a microtubule-associated protein, with a strong influence on both the morphology and physiology of neurons. In AD, tau protein undergoes post-translational modifications, which could play a relevant role in the onset and progression of this disease. Also, these abnormal forms of tau could be present during the physiological aging that could be related to memory impairment present during this stage. We previously showed that tau ablation improves mitochondrial function and cognitive abilities in young wild-type mice. However, the possible contribution of tau during aging that could predispose to the development of AD is unclear. Here, we show that tau deletion prevents cognitive impairment and improves mitochondrial function during normal aging as indicated by a reduction in oxidative damage and increased ATP production. Notably, we observed a decrease in cyclophilin-D (CypD) levels in aged tau-/- mice, resulting in increased calcium buffering and reduced mitochondrial permeability transition pore (mPTP) opening. The mPTP is a mitochondrial structure, whose opening is dependent on CypD expression, and new evidence suggests that this could play an essential role in the neurodegenerative process showed during AD. In contrast, hippocampal CypD overexpression in aged tau-/- mice impairs mitochondrial function evidenced by an ATP deficit, increased mPTP opening, and memory loss; all effects were observed in the AD pathology. Our results indicate that the absence of tau prevents age-associated cognitive impairment by maintaining mitochondrial function and reducing mPTP opening through a CypD-dependent mechanism. These findings are novel and represent an important advance in the study of how tau contributes to the cognitive and mitochondrial failure present during aging and AD in the brain.
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    Wnt-5a Signaling Mediates Metaplasticity at Hippocampal CA3-CA1 Synapses in Mice
    (2024) Parodi, Jorge; Mira, Rodrigo G.; Fuenzalida, Marco; Cerpa, Waldo; Serrano, Felipe G.; Tapia-Rojas, Cheril; Martinez-Torres, Ataulfo; Inestrosa, Nibaldo C.
    Wnt signaling plays a role in synaptic plasticity, but the specific cellular events and molecular components involved in Wnt signaling-mediated synaptic plasticity are not well defined. Here, we report a change in the threshold required to induce synaptic plasticity that facilitates the induction of long-term potentiation (LTP) and inhibits the induction of long-term depression (LTD) during brief exposure to the noncanonical ligand Wnt-5a. Both effects are related to the metaplastic switch of hippocampal CA3-CA1 synaptic transmission, a complex mechanism underlying the regulation of the threshold required to induce synaptic plasticity and of synaptic efficacy. We observed an early increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) that persisted over time, including after washout. The first phase involves an increase in the fEPSP amplitude that is required to trigger a spontaneous second phase that depends on Jun N-terminal kinase (JNK) and N-methyl D-aspartate receptor (NMDAR) activity. These changes are prevented by treatment with secreted frizzled-related protein 2 (sFRP-2), an endogenous antagonist of Wnt ligands. Here, we demonstrate the contribution of Wnt-5a signaling to a process associated with metaplasticity at CA3-CA1 synapses that favors LTP over LTD.