Neuroprotective role of PKD1 against ischemic and kainic acid-induced brain injury

Trabajo presentado en el Second Spanish Molecular Imaging Network (SMIN) Meeting, celebrado en Madrid (España) el 26 de febrero de 2018

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-kappa B/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-kappa B/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Development and plasticity of the corpus callosum

© 2020. Published by The Company of Biologists LtdThe corpus callosum (CC) connects the cerebral hemispheres and is the major mammalian commissural tract. It facilitates bilateral sensory integration and higher cognitive functions, and is often affected in neurodevelopmental diseases. Here, we review the mechanisms that contribute to the development of CC circuits in animal models and humans. These species comparisons reveal several commonalities. First, there is an early period of massive axonal projection. Second, there is a postnatal temporal window, varying between species, in which early callosal projections are selectively refined. Third, sensory-derived activity influences axonal refinement. We also discuss how defects in CC formation can lead to mild or severe CC congenital malformations.his work was funded by grants from ERA-Net Neuron, the European Union and the Ministerio de Economı́a, Industria y Competitividad de España (ERA-Net Neuron/PCIN-2015-176-C02-02); from the Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, European Union (SAF2017-83117-R and RED2018-102553T); and from the European Union, FLAG-ERA-Human Brain Project, Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, European Union (PCI2019- 111872-2)

PKD is regulated in excitotoxic conditions

Trabajo presentado al 1st Spanish Molecular Imaging Network (SMIN) Meeting, celebrado en Madrid el 30 de enero dew 2017.Peer Reviewe

Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.L.B.-G. and A.A. hold fellowships from the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie (grant agreement no. 713673) and the “La Caixa” Foundation [ID 100010434; the fellowship codes are LCF/BQ/IN17/11620044 (L.B.-G.) and LCF/BQ/DI21/11860049 (A.A.)]. C.G.-A. holds a fellowship funded by MCIU/AEI/10.13039/501100011033 and by ESF “Investing in your future” (BES-2017-080303), and P.C. and A.S.-C. were funded by fellowships from MICIU (PRE2021-099425 and FJC2021-047621-I, respectively). G.P. acknowledges funding from La Marató TV3 Foundation (nos. 225619) and PID2019-106579RB-I00 from MCIU/AEI/10.13039/501100011033. M.N. acknowledges funding from SAF2017-83117-R funded by MCIU/AEI/10.13039/501100011033; “ERDF A way of making Europe” funded by the “European Union”; PID2020-112831GB-I00 funded by MCIU/AEI/10.13039/501100011033; and PEJ-2021-TL/BMD-22114 funded by “la Consejería de Educación, Universidades, Ciencia y Portavocía,” de la Comunidad de Madrid. F.L. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement number 949652) also supporting N.S.D.L.R, the Valencian Community (CIDEGENT), and the “Severo Ochoa Centers of Excellence” from the MICIU.Peer reviewe

The role of PKD1 in brain injury: ROS detoxification and neuroprotection

Resumen del trabajo presentado al 1st PhD Research Symposium in Health Sciences and Biomedicine, celebrado en la Universidad Autónoma de Madrid el 18 de mayo de 2018.Peer reviewe

Mechanisms of PKD inactivation in excitotoxic brain damage: How PKD activity protects neurons from death

Trabajo presentado al 17 National Congress of the Spanish Society of Neuroscience (SENC), celebrado en Alicante (España) del 27 al 30 de septiembre de 2017.Peer Reviewe

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-kappa B/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-kappa B/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders