Browsing by Author "Godoy Zeballos, Juan Alejandro"

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    Amyloid-beta Peptide Fibrils Induce Nitro-Oxidative Stress in Neuronal Cells
    (2010) Ill-Raga, G.; Godoy Zeballos, Juan Alejandro; Belmar Lucero, Sebastián Antoni; Cerpa Nebott, Waldo Francisco
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    ATP Induces NO Production in Hippocampal Neurons by P2X(7) Receptor Activation Independent of Glutamate Signaling
    (2013) Codocedo Henríquez, Juan Francisco.; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
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    Canonical Wnt signaling protects hippocampal neurons from A beta oligomers: role of non-canonical Wnt-5a/Ca2+ in mitochondrial dynamics
    (2013) Silva Alvarez, Carmen.; Arrazola Tello, Macarena Soledad.; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
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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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    Morphological neurite changes induced by porcupine inhibition are rescued by Wnt ligands
    (2021) Godoy Zeballos, Juan Alejandro; Espinoza Caicedo, Jasson Amadeus; Inestrosa Cantín, Nibaldo
    Abstract Background Wnt signaling plays key roles in cellular and physiological processes, including cell proliferation, differentiation and migration during development and tissue homeostasis in adults. This pathway can be defined as Wnt/β-catenin-dependent or β-catenin-independent or “non-canonical”, both signaling are involved in neurite and synapse development/maintenance. Porcupine (PORCN), an acylase that o-acylates Wnt ligands, a major modification in secretion and interaction with its receptors. We use Wnt-C59, a specific PORCN inhibitor, to block the secretion of endogenous Wnts in embryonic hippocampal neurons (DIV 4). Under these conditions, the activity of exogenous Wnt ligands on the complexity of the dendritic tree and axonal polarity were evaluated Methods Cultured primary embryonic hippocampal neurons obtained from Sprague–Dawley rat fetuses (E18), were cultured until day in vitro (DIV) 4 (according to Banker´s protocol) and treated with Wnt-C59 for 24 h, Wnt ligands were added to the cultures on DIV 3 for 24 h. Dendritic arbors and neurites were analysis by fluorescence microscopy. Transfection with Lipofectamine 2000 on DIV 2 of plasmid expressing eGFP and KIF5-Cherry was carried out to evaluate neuronal polarity. Immunostaining was performed with MAP1B and Tau protein. Immunoblot analysis was carried out with Wnt3a, β-catenin and GSK-3β (p-Ser9). Quantitative analysis of dendrite morphology was carried out with ImageJ (NIH) software with Neuron J Plugin. Results We report, here, that Wnt-C59 treatment changed the morphology of the dendritic arbors and neurites of embryonic hippocampal neurons, with decreases β-catenin and Wnt3a and an apparent increase in GSK-3β (p-Ser9) levels. No effect was observed on axonal polarity. In sister cultures, addition of exogenous Wnt3a, 5a and 7a ligands rescued the changes in neuronal morphology. Wnt3a restored the length of neurites to near that of the control, but Wnt7a increased the neurite length beyond that of the control. Wnt5a also restored the length of neurites relative to Wnt concentrations. Conclusions Results indicated that Wnt ligands, added exogenously, restored dendritic arbor complexity in embryonic hippocampal neurons, previously treated with a high affinity specific Porcupine inhibitor. We proposed that PORCN is an emerging molecular target of interest in the search for preclinical options to study and treat Wnt-related diseases. Video Abstract
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    Multiple Cryptosporidium parvum subtypes detected in a unique isolate of a Chilean neonatal calf with diarrhea
    (2015) Mercado, Rubén; Peña, Sebastián; Shozo Ozaki, Luiz; Fredes, Fernando; Godoy Zeballos, Juan Alejandro
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    Nicotine Modulates Mitochondrial Dynamics in Hippocampal Neurons
    (2018) Godoy Zeballos, Juan Alejandro; Valdivieso, Angel G.; Inestrosa Cantín, Nibaldo
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    Nicotine Prevents Synaptic Impairment Induced by Amyloid-beta Oligomers Through alpha 7-Nicotinic Acetylcholine Receptor Activation
    (2013) Inestrosa Cantín, Nibaldo; Godoy Zeballos, Juan Alejandro; Vargas, J.; Arrazola, M.; Ríos Leal, Juvenal Antonio; Carvajal, F.; Serrano, F.; Farías, G.
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    Phosphorylated tau potentiates A beta-induced mitochondrial damage in mature neurons
    (2014) Quintanilla Gómez, Rodrigo Arthur; Bernhardi Montgomery, Rommy von; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
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    Role of Sirt1 During the Ageing Process: Relevance to Protection of Synapses in the Brain
    (2014) Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
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    Signaling pathway cross talk in Alzheimer's disease
    (2014) Godoy Zeballos, Juan Alejandro; Ríos Leal, Juvenal Antonio; Inestrosa Cantín, Nibaldo
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    Tetrahydrohyperforin Decreases Cholinergic Markers associated with Amyloid-beta Plaques, 4-Hydroxynonenal Formation, and Caspase-3 Activation in A beta PP/PS1 Mice
    (2013) Carvajal, F.; Zolezzi, J.; Tapia, C.; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
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    The Exocyst Component Exo70 Modulates Dendrite Arbor Formation, Synapse Density, and Spine Maturation in Primary Hippocampal Neurons
    (2019) Lira, M.; Arancibia, D.; Orrego, P. R.; Montenegro Venegas, C.; Cruz, Y.; García, J.; Leal Ortiz, S.; Godoy Zeballos, Juan Alejandro; Gundelfinger, E. D.; Inestrosa Cantín, Nibaldo; Garner, C. C.; Zamorano, P.; Torres, V. I.
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    Thiazolidinediones Promote Axonal Growth through the Activation of the JNK Pathway
    (2013) Quintanilla Gómez, Rodrigo Arthur; Godoy Zeballos, Juan Alejandro; Alfaro, I.; Cabezas, D.; Bernhardi Montgomery, Rommy von; Bronfman A., Miguel L.; Inestrosa Cantín, Nibaldo
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    Wnt-5 alpha increases NO and modulates NMDA receptor in rat hippocampal neurons
    (2014) Munoz, Francisco; Godoy Zeballos, Juan Alejandro; Cerpa Nebott, Waldo Francisco; Poblete, I.; García-Huidobro Toro, Juan Pablo; Inestrosa Cantín, Nibaldo
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    Wnt-5a Ligand Modulates Mitochondrial Fission-Fusion in Rat Hippocampal Neurons
    (2014) Godoy Zeballos, Juan Alejandro; Arrazola Tello, Macarena Soledad.; Inestrosa Cantín, Nibaldo
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    Wnt-5a occludes A beta oligomer-induced depression of glutamatergic transmission in hippocampal neurons
    (2010) Cerpa Nebott, Waldo Francisco; Farías Galdames, Ginny Cheryl.; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
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    Wnt-5aoccludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons
    (2010) Cerpa Nebott, Waldo Francisco; Farías Galdames, Ginny Cheryl.; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo; Fuenzalida, Marco.; Bonansco, Christian.
    Abstract Background Soluble amyloid-β (Aβ;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation. Results We report here that the Wnt signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Aβ oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Aβ oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Aβ oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Aβ oligomers inversely modulate postsynaptic components. Conclusion These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.Abstract Background Soluble amyloid-β (Aβ;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation. Results We report here that the Wnt signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Aβ oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Aβ oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Aβ oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Aβ oligomers inversely modulate postsynaptic components. Conclusion These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.
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    Wnt3a ligand facilitates autophagy in hippocampal neurons by modulating a novel GSK-3β-AMPK axis
    (2018) Ríos Leal, Juvenal Antonio; Godoy Zeballos, Juan Alejandro; Inestrosa Cantín, Nibaldo
    Abstract Background In the adult central nervous system (CNS), Wnt signaling regulates dendritic structure and synaptic plasticity. The Wnt signaling pathway can be divided into the canonical (β-catenin-dependent) and non-canonical pathways. In the canonical pathway, the binding of canonical ligands such as Wnt3a to the Frizzled receptor induces inactivation of glycogen synthase kinase-3β (GSK-3β), which stabilizes β-catenin and allows its translocation to the nucleus. However, to date, few studies have focused on β-catenin-independent Wnt signaling or explained the underlying mechanisms connecting Wnt signaling to cellular energy metabolism. A recent study demonstrated negative regulation of 5′ adenosine monophosphate-activated protein kinase (AMPK), a major target of GSK-3β that regulates cellular metabolism under diverse conditions. Mainly based on these observations, we evaluated whether Wnt3a ligand modulates autophagy by regulating the GSK-3β/AMPK axis. Methods Cultured primary hippocampal neurons and slices of the CA1 region of rat hippocampus were used. GSK-3β inhibition, AMPK activation, PP2Ac expression, and LC3 processing were examined by western blotting. Autophagic compartments were studied using the CYTO-ID® fluorescent probe, and mature autophagosomes were observed via transmission electron microscopy (TEM). Results Wnt3a ligand, acting through the Frizzled receptor, promotes the rapid activation of AMPK by inactivating GSK-3β. Biochemical analysis of downstream targets indicated that Wnt3a ligand modulates autophagy in hippocampal neurons. Conclusions Our results revealed new aspects of Wnt signaling in neuronal metabolism. First, AMPK is an additional target downstream of the Wnt cascade, suggesting a molecular mechanism for the metabolic effects previously observed for Wnt signaling. Second, this mechanism is independent of β-catenin, suggesting a relevant role for non-genomic activity of the Wnt pathway in cellular metabolism. Finally, these results have new implications regarding the role of Wnt signaling in the modulation of autophagy in neurons, with a possible role in the removal of accumulated intracellular proteins.Abstract Background In the adult central nervous system (CNS), Wnt signaling regulates dendritic structure and synaptic plasticity. The Wnt signaling pathway can be divided into the canonical (β-catenin-dependent) and non-canonical pathways. In the canonical pathway, the binding of canonical ligands such as Wnt3a to the Frizzled receptor induces inactivation of glycogen synthase kinase-3β (GSK-3β), which stabilizes β-catenin and allows its translocation to the nucleus. However, to date, few studies have focused on β-catenin-independent Wnt signaling or explained the underlying mechanisms connecting Wnt signaling to cellular energy metabolism. A recent study demonstrated negative regulation of 5′ adenosine monophosphate-activated protein kinase (AMPK), a major target of GSK-3β that regulates cellular metabolism under diverse conditions. Mainly based on these observations, we evaluated whether Wnt3a ligand modulates autophagy by regulating the GSK-3β/AMPK axis. Methods Cultured primary hippocampal neurons and slices of the CA1 region of rat hippocampus were used. GSK-3β inhibition, AMPK activation, PP2Ac expression, and LC3 processing were examined by western blotting. Autophagic compartments were studied using the CYTO-ID® fluorescent probe, and mature autophagosomes were observed via transmission electron microscopy (TEM). Results Wnt3a ligand, acting through the Frizzled receptor, promotes the rapid activation of AMPK by inactivating GSK-3β. Biochemical analysis of downstream targets indicated that Wnt3a ligand modulates autophagy in hippocampal neurons. Conclusions Our results revealed new aspects of Wnt signaling in neuronal metabolism. First, AMPK is an additional target downstream of the Wnt cascade, suggesting a molecular mechanism for the metabolic effects previously observed for Wnt signaling. Second, this mechanism is independent of β-catenin, suggesting a relevant role for non-genomic activity of the Wnt pathway in cellular metabolism. Finally, these results have new implications regarding the role of Wnt signaling in the modulation of autophagy in neurons, with a possible role in the removal of accumulated intracellular proteins.Abstract Background In the adult central nervous system (CNS), Wnt signaling regulates dendritic structure and synaptic plasticity. The Wnt signaling pathway can be divided into the canonical (β-catenin-dependent) and non-canonical pathways. In the canonical pathway, the binding of canonical ligands such as Wnt3a to the Frizzled receptor induces inactivation of glycogen synthase kinase-3β (GSK-3β), which stabilizes β-catenin and allows its translocation to the nucleus. However, to date, few studies have focused on β-catenin-independent Wnt signaling or explained the underlying mechanisms connecting Wnt signaling to cellular energy metabolism. A recent study demonstrated negative regulation of 5′ adenosine monophosphate-activated protein kinase (AMPK), a major target of GSK-3β that regulates cellular metabolism under diverse conditions. Mainly based on these observations, we evaluated whether Wnt3a ligand modulates autophagy by regulating the GSK-3β/AMPK axis. Methods Cultured primary hippocampal neurons and slices of the CA1 region of rat hippocampus were used. GSK-3β inhibition, AMPK activation, PP2Ac expression, and LC3 processing were examined by western blotting. Autophagic compartments were studied using the CYTO-ID® fluorescent probe, and mature autophagosomes were observed via transmission electron microscopy (TEM). Results Wnt3a ligand, acting through the Frizzled receptor, promotes the rapid activation of AMPK by inactivating GSK-3β. Biochemical analysis of downstream targets indicated that Wnt3a ligand modulates autophagy in hippocampal neurons. Conclusions Our results revealed new aspects of Wnt signaling in neuronal metabolism. First, AMPK is an additional target downstream of the Wnt cascade, suggesting a molecular mechanism for the metabolic effects previously observed for Wnt signaling. Second, this mechanism is independent of β-catenin, suggesting a relevant role for non-genomic activity of the Wnt pathway in cellular metabolism. Finally, these results have new implications regarding the role of Wnt signaling in the modulation of autophagy in neurons, with a possible role in the removal of accumulated intracellular proteins.