Browsing by Author "Ampuero, Estibaliz"

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    Evidence for TGF-β1/Nrf2 Signaling Crosstalk in a Cuprizone Model of Multiple Sclerosis
    (2024) Guevara, Coram; Vicencio, Sinay C.; Pizarro, Ignacio S.; Villavicencio-Tejo, Francisca; Quintanilla, Rodrigo A.; Astudillo, Pablo; Ampuero, Estibaliz; Varas, Rodrigo; Orellana, Juan A.; Ortiz, Fernando C.
    Multiple sclerosis (MS) is a chronic and degenerative disease that impacts central nervous system (CNS) function. One of the major characteristics of the disease is the presence of regions lacking myelin and an oxidative and inflammatory environment. TGF-beta 1 and Nrf2 proteins play a fundamental role in different oxidative/inflammatory processes linked to neurodegenerative diseases such as MS. The evidence from different experimental settings has demonstrated a TGF-beta 1-Nrf2 signaling crosstalk under pathological conditions. However, this possibility has not been explored in experimental models of MS. Here, by using the cuprizone-induced demyelination model of MS, we report that the in vivo pharmacological blockage of the TGF-beta 1 receptor reduced Nrf2, catalase, and TGF beta-1 protein levels in the demyelination phase of cuprizone administration. In addition, ATP production, locomotor function and cognitive performance were diminished by the treatment. Altogether, our results provide evidence for a crosstalk between TGF-beta 1 and Nrf2 signaling pathways under CNS demyelination, highlighting the importance of the antioxidant cellular response of neurodegenerative diseases such as MS.
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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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    PSD95 regulates morphological development of adult-born granule neurons in the mouse hippocampus
    (2019) Mardones, Muriel D.; Jorquera, Patricia, V; Herrera-Soto, Andrea; Ampuero, Estibaliz; Bustos, Fernando J.; van Zundert, Brigitte; Varela-Nallar, Lorena
    In the adult hippocampus new neurons are generated in the dentate gyrus from neural progenitor cells. Adult-born neurons integrate into the hippocampal circuitry and contribute to hippocampal function. PSD95 is a major postsynaptic scaffold protein that is crucial for morphological maturation and synaptic development of hippocampal neurons. Here we study the function of PSD95 in adult hippocampal neurogenesis by downregulating PSD95 expression in newborn cells using retroviral-mediated RNA interference. Retroviruses coding for a control shRNA or an shRNA targeting PSD95 (shPSD95) were stereotaxically injected into the dorsal dentate gyms of 2-month-old C57BL/6 mice. PSD95 knockdown did not affect neuronal differentiation of newborn cells into neurons, or migration of newborn neurons into the granule cell layer. Morphological analysis revealed that newborn neurons expressing shPSD95 showed increased dendritic length and increased number of high-order dendrites. Concomitantly, dendrites from shPSD95-expressing newborn granule neurons showed a reduction in the density of dendritic spines. These results suggest that PSD95 is required for proper dendritic and spine maturation of adult-born neurons, but not for early stages of neurogenesis in the hippocampus.