Browsing by Author "Parodi, Jorge"

Now showing 1 - 6 of 6
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    Pathogenicity of lupus anti-ribosomal P antibodies : Role of cross-reacting neuronal surface P antigen in glutamatergic transmission and plasticity in a mouse model
    (2015) Segovia Miranda, Fabián; Serrano, Felipe; Dyrda, Agnieszka; Ampuero, Estibaliz; Retamal, Claudio; Bravo Zehnder, Marcela; Parodi, Jorge; Zamorano, Pedro; Valenzuela, David; Massardo Vega, Loreto; Van Zundert, Brigitte; Inestrosa Cantín, Nibaldo; González Alfonso
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    Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses
    (NATL ACAD SCIENCES, 2010) Varela Nallar, Lorena; Alfaro, Ivan E.; Serrano, Felipe G.; Parodi, Jorge; Inestrosa, Nibaldo C.
    Growing evidence indicates that Wingless-type (Wnt) signaling plays an important role in the maturation of the central nervous system. We report here that Wingless-type family member 5A (Wnt-5a) is expressed early in development and stimulates dendrite spine morphogenesis, inducing de novo formation of spines and increasing the size of the preexisting ones in hippocampal neurons. Wnt-5a increased intracellular calcium concentration in dendritic processes and the amplitude of NMDA spontaneous miniature currents. Acute application of Wnt-5a increased the amplitude of field excitatory postsynaptic potentials (fEPSP) in hippocampal slices, an effect that was prevented by calcium-channel blockers. The physiological relevance of our findings is supported by studies showing that Wnt scavengers decreased spine density, miniature excitatory postsynaptic currents, and fEPSP amplitude. We conclude that Wnt-5a stimulates different aspects of synaptic differentiation and plasticity in the mammalian central nervous system.
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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.
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    Wnt-5a/Ca2+pathway modulates endogenous current and oocyte structure of Xenopus laevis
    (2024) Parodi, Jorge; Mira, Rodrigo G.; Martinez-Torres, Ataulfo; Inestrosa, Nibaldo C.
    Wnt signaling plays an essential role in cellular processes like development, maturation, and function maintenance. Xenopus laevis oocytes are a suitable model to study not only the development but also the function of different receptors expressed in their membranes, like those receptors expressed in the central nervous system (CNS) including Frizzled 7. Here, using frog oocytes and recordings of endogenous membrane currents in a two- electrode path configuration along with morphological observations, we evaluated the role of the non-canonical Wnt-5a ligand in oocytes. We found that acute application of Wnt-5a generated changes in endogenous calcium- dependent currents, entry oscillatory current, the membrane's outward current, and induced membrane depolarization. The incubation of oocytes with Wnt-5a caused a reduction of the membrane potential, potassium outward current, and protected the ATP current in the epithelium/theca removed (ETR) model. The oocytes exposed to Wnt-5a showed increased viability and an increase in the percentage of the germinal vesicle breakdown (GVBD), at a higher level than the control with progesterone. Altogether, our results suggest that Wnt-5a modulates different aspects of oocyte structure and generates calcium-dependent endogenous current alteration and GVDB process with a change in membrane potential at different concentrations and times of the exposition. These results help to understand the cellular effect of Wnt-5a and present the use of Xenopus oocytes to explore the mechanism that could impact the activation of Wnt signaling.
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    Wnt5a inhibits K+ currents in hippocampal synapses through nitric oxide production
    (2015) Parodi, Jorge; Montecinos Oliva, Carla; Varas, Rodrigo; Alfaro, Iván E.; Serrano, Felipe G.; Varas Godoy, Manuel; Muñoz, Francisco J.; Cerpa Nebott, Waldo Francisco; Godoy, Juan A.; Inestrosa Cantín, Nibaldo
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    β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure
    (2010) Parodi, Jorge; Sepulveda, Fernando J.; Roa, Jorge; Opazo, Carlos; Inestrosa, Nibaldo C.; Aguayo, Luis G.
    Alzheimer disease is a progressive neurodegenerative brain disorder that leads to major debilitating cognitive deficits. It is believed that the alterations capable of causing brain circuitry dysfunctions have a slow onset and that the full blown disease may take several years to develop. Therefore, it is important to understand the early, asymptomatic, and possible reversible states of the disease with the aim of proposing preventive and disease-modifying therapeutic strategies. It is largely unknown how amyloid beta-peptide (A beta), a principal agent in Alzheimer disease, affects synapses in brain neurons. In this study, we found that similar to other pore-forming neurotoxins, A beta induced a rapid increase in intracellular calcium and miniature currents, indicating an enhancement in vesicular transmitter release. Significantly, blockade of these effects by low extracellular calcium and a peptide known to act as an inhibitor of the A beta-induced pore prevented the delayed failure, indicating that A beta blocks neurotransmission by causing vesicular depletion. This new mechanism for A beta synaptic toxicity should provide an alternative pathway to search for small molecules that can antagonize these effects of A beta.