Gonzalo M. Sánchez

Uppsala University

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Olof Idevall‐Hagren

Uppsala University

Edgar Kornisiuk

University of Buenos Aires

CČ

Carlos Červeñanský

Instituto de Investigaciones Biológicas Clemente Estable

Diana Jerusalinsky

University of Buenos Aires

Jorge Alberto Quillfeldt

Universidade Federal do Rio Grande do Sul

Carlos Blanco

University of Buenos Aires

Ceren Incedal Nilsson

Uppsala University

Edmund S. Meltzer

University of Wisconsin–Stevens Point

Johan Kreuger

Uppsala University

Fernándo Carlos Pellegrino

University of Buenos Aires

Cooperative Institutions

University of Buenos Aires

Consejo Nacional de Investigaciones Científicas y Técnicas

Fundación Ciencias Exactas y Naturales

Uppsala University

Universidade Federal do Rio Grande do Sul

Institute of Astronomy and Space Physics

Centro Científico Tecnológico - San Juan

Linköping University

Centre National de la Recherche Scientifique

National Agricultural Technology Institute

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Piezo1 activation attenuates thrombin-induced blebbing in breast cancer cells

bioRxiv (Cold Spring Harbor Laboratory) (2020)

P.W. O’Callaghan Adam Engberg Nikos Fatsis-Kavalopoulos Gonzalo M. Sánchez Olof Idevall‐Hagren

Abstract Cancer cells exploit a variety of migration modes to leave primary tumors and establish metastases, including amoeboid cell migration facilitated by bleb formation. Here we demonstrate that thrombin induces dynamic blebbing in the MDA-MB-231 breast cancer cell line, and confirm that PAR2 activation is sufficient to induce this effect. Cell confinement has been implicated as a driving force in bleb-based migration. Unexpectedly, we find that gentle contact compression, exerted using a “Cell Press” to mechanically stimulate cells, attenuated thrombin-induced blebbing with an associated increase in cytosolic calcium. Thrombin-induced blebbing was similarly attenuated using Yoda1, an agonist of the mechanosensitive calcium channel Piezo1, and its capacity to attenuate blebbing was impaired in Piezo1 depleted cells. Additionally, Piezo1 activation suppressed and reversed the thrombin-induced phosphorylation of ERM proteins, which are implicated in the blebbing process, and this activity was in part mediated through activation of the PP1A/PP2A family of serine/threonine phosphatases. Our results provide mechanistic insights into Piezo1 activation as a suppressor of dynamic blebbing, specifically that which is induced by thrombin.

Piezo1

Bleb (medicine)

10.1101/2020.04.30.068338

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Citations (4)

Revisión Anatómica del Músculo Bíceps Femoral del Canino

International Journal of Morphology (2010)

Carlos Alberto Arzone Carlos Blanco Pablo Genoud Fernándo Carlos Pellegrino Gonzalo M. Sánchez

actuando en la flexoextensión de la articulación femorotibiorotuliana y la abducción del miembro.La evaluación correcta de su función es importante en la clínica veterinaria.Existen puntos controversiales entre los autores consultados acerca de la morfología de este músculo.El presente estudio tiene como objetivo discutir las distintas descripciones, reparando en las inserciones, la estructura e inervación del músculo.Se han realizado las disecciones bilaterales en 12 animales.La conservación de las piezas se realizó por inmersión en piletas, con una dilución de formol al 10 % y ácido fenico al 4% en agua.Se utilizaron diferentes técnicas de abordaje al músculo en cuestión, para obtener distintas observaciones de las estructuras.Se halló que el músculo BF se origina por medio de dos cabezas, como queda implícito en su denominación, una cabeza craneal, más voluminosa y una cabeza caudal más pequeña.La primera originada en el ligamento sacrotuberal y en la superficie lateral de la tuberosidad isquiática.La cabeza caudal, se origina de la tuberosidad isquiática.Estas partes a pesar de hallarse estrechamente unidas se individualizan a nivel de los vientres musculares por medio de una delgada lámina de tejido conectivo que se extiende hasta el tercio distal del músculo.Respecto a la inervación, no se encontraron ramas del nervio glúteo caudal que inerven las partes al músculo.

10.4067/s0717-95022010000400026

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On the ictogenic properties of the piriform cortex in vitro

Epilepsia (2012)

Gabriella Panuccio Gonzalo M. Sánchez Maxime Lévesque Pariya Salami Marco de Curtis

Summary Purpose: The piriform cortex (PC) is known to be epileptic‐prone and it may be involved in the manifestation of limbic seizures. Herein, we have characterized some electrophysiologic and pharmacologic properties of the spontaneous epileptiform activity generated by PC networks maintained in vitro. Methods: We performed field potential recordings from the PC in coronal or sagittal rat brain slices along with pharmacologic manipulations of γ‐aminobutyric acid (GABA)ergic and glutamatergic signaling during application of the convulsant drug 4‐aminopyridine (4AP, 50 μ m ). Key Findings: Coronal and sagittal preparations generated interictal‐like and ictal‐like epileptiform discharges with similar duration and frequency. Ictal‐like discharges in sagittal slices were initiated mostly in the PC anterior subregion, whereas interictal activity did not have any preferential site of origin. In sagittal slices, high frequency oscillations (HFOs) at 80–200 Hz were detected mainly at the beginning of the ictal discharge in both posterior and anterior subregions. N ‐Methyl‐ d ‐aspartate (NMDA) receptor antagonism abolished ictal discharges, but failed to influence interictal activity. In the absence of ionotropic glutamatergic transmission, PC networks generated slow, GABA receptor–dependent events. Finally, GABA A receptor antagonism during application of 4AP only, abolished ictal discharges and disclosed recurrent interictal activity. Significance: Our findings demonstrate that PC networks can sustain in vitro epileptiform activity induced by 4AP. HFOs, which emerge at the onset of ictal activity, may be involved in PC ictogenesis. As reported in several cortical structures, ionotropic glutamatergic neurotransmission is necessary but not sufficient for ictal discharge generation, a process that also requires operative GABA A receptor–mediated signaling.

Piriform cortex

10.1111/j.1528-1167.2012.03408.x

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Citations (31)

M₄ muscarinic receptors are involved in modulation of neurotransmission at synapses of Schaffer collaterals on CA1 hippocampal neurons in rats

Journal of Neuroscience Research (2008)

Gonzalo M. Sánchez Lucas de Oliveira Alvares María Victoria Oberholzer Bruna Pasqualini Genro Jorge Alberto Quillfeldt

Abstract All five subtypes of muscarinic acetylcholine receptors (mAChR; M 1 –M 5 ) are expressed in the hippocampus, where they are involved both in cognitive functions and in synaptic plasticity, such as long‐term potentiation (LTP). Muscarinic toxins (MTs) are small proteins from mamba snake venoms that display exquisite discrimination between mAChRs. MT1 acts as an agonist at M 1 and an antagonist at M 4 receptors, with similar affinities for both. MT3, the most selective antagonist available for M 4 receptors, infused into the CA1 region immediately after training caused amnesia in the rat, indicating the participation of M 4 receptors in memory consolidation. Our goal was to investigate the participation of M 4 receptor in neurotransmission at the hippocampal Schaffer collaterals‐CA1 synapses. Two different preparations were used: 1) field potential recordings in freshly prepared rat hippocampal slices with high‐frequency stimulation to induce potentiation and 2) whole‐cell voltage clamp in cultured hippocampal organotypic slices with paired stimuli. In preparation 1, a dose of MT3 that was previously shown to cause amnesia blocked LTP; the nonselective antagonist scopolamine blocked LTP without affecting basal transmission, although it was depressed with higher concentration. In preparation 2, basal transmission was decreased and LTP induction was prevented by an MT3 concentration that would bind mainly to M 4 receptors. Although M 1 receptors appeared to modulate transmission positively at these excitatory synapses, M 1 activation concomitant with M 4 blockade (by MT1) only allowed a brief, short‐term potentiation. Accordingly, M 4 blockade by MT3 strongly supports a permissive role of M 4 receptors and suggests their necessary participation in synaptic plasticity at these synapses. © 2008 Wiley‐Liss, Inc.

Schaffer collateral

10.1002/jnr.21876

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Citations (28)

The Edwin Smith Papyrus

Gonzalo M. Sánchez Edmund S. Meltzer

This volume contains the original hieratic text, complete transcription into hieroglyphs, transliteration, English translation, philological apparatus and copiously illustrated medical commentaries for the forty-eight clinical cases of the Edwin Smith Papyrus, as well as extensive bibliographical resources, and a lucid introduction exploring the importance of the document, the history of previous scholarship, and distinctive aspects of the current edition. It offers an authoritative treatment of the Egyptian text, which clarifies the meaning of many passages from the papyrus and points the way to their correct medical interpretation. The Edwin Smith Papyrus (ESP) is the first comprehensive trauma treatise in the history of medicine. Not only is the ESP the source of numerous anatomical and functional concepts of the nervous system, it is the basis for the development of modern objective clinical thinking, establishing the foundations of modern medicine more than a thousand years before Hippocrates. The volume features an impressive array of medical material that reveals the precise conditions described by the ancient physician and explores the Egyptian contribution to modern diagnostics, clinical practice, and methodology. This publication sets the standard in the presentation of ancient medical documents. It also includes the previously unpublished translation of the papyrus by Edwin Smith himself.

Papyrus

Transliteration

Presentation (obstetrics)

10.5913/2012017

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Citations (9)

Snake Identification in the Ancient Egyptian Brooklyn Medical Papyrus

Gonzalo M. Sánchez Edmund S. Meltzer Wolfgang Wüster Nicholas R. Casewell Gordon W. Schuett

Papyrus

Identification

10.2307/jj.15507130

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Reduction of an Afterhyperpolarization Current Increases Excitability in Striatal Cholinergic Interneurons in Rat Parkinsonism

Journal of Neuroscience (2011)

Gonzalo M. Sánchez Mariano Julián Rodriguez Pablo E. Pomata Lorena Rela M. Gustavo Murer

Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response to appetitive and aversive events and to environmental cues that have predicted these events during learning. Notably, the pause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of I(sAHP), a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that I(sAHP) induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces I(sAHP) and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, a reduction of I(sAHP) may alter synchronization of cholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.

Afterhyperpolarization

Interneuron

10.1523/jneurosci.6345-10.2011

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Citations (53)

Locally released somatostatin triggers cAMP and Ca2+ signaling in primary cilia to modulate pancreatic β-cell function

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Ceren Incedal Nilsson Özge Dumral Gonzalo M. Sánchez Beichen Xie Andreas Müller

ABSTRACT Somatostatin is produced and released from δ-cells within pancreatic islets of Langerhans and constitutes one of the most important negative regulators of islet hormone secretion. Somatostatin receptors (SSTR) are abundantly expressed in the islet cells and coupled to Gαi and lowering of intracellular cAMP. We find that both SSTR3 and SSTR5 localize to primary cilia of β-cells, and that activation of these receptors lowers the ciliary cAMP concentration. cAMP produced in the cytosol can enter the cilium through diffusion, but activation of ciliary SSTR3 specifically counteracts the rise of cAMP in the cilium. Moreover, we find that islet δ-cells are positioned near primary cilia of the other islet cell types and that somatostatin secretion is directed towards primary cilia. While acute exposure to somatostatin caused a rapid lowering of ciliary cAMP, sustained exposure promoted nuclear entry of the cilia-dependent transcription factor GLI2 through a mechanism that operated in parallel with the canonical Hedgehog pathway and depended on ciliary Ca 2+ signaling. We also find that primary cilia length is reduced in islets from human donors with type-2 diabetes, which is associated with a reduction in cilia-δ-cell interactions. Our findings show that islet cell primary cilia constitute an important target of somatostatin action that endows it with the ability to regulate islet cell function beyond the acute suppression of hormone release.

Primary (astronomy)

Somatostatin receptor 3

10.1101/2024.06.05.597562

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Citations (1)

Facilitatory effect of the intra-hippocampal pre-test administration of MT3 in the inhibitory avoidance task

Behavioural Brain Research (2006)

Felipe Diehl L FURSTENAUDEOLIVEIRA Gonzalo M. Sánchez C CAMBOIM Lucas de Oliveira Alvares

10.1016/j.bbr.2006.11.030

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Citations (19)

CRITERIOS DE HOMOLOGACION ENTRE LAS CINTURAS ESCAPULAR Y PELVICA Y SUS ESTRUCTURAS ASOCIADAS

Revista chilena de anatomía (1998)

Fernándo Carlos Pellegrino C. Tangelson L. Galliano L. Trevisan Gonzalo M. Sánchez

The waists are studied customarily in separated form together with the corresponding member. The muscles associated with them are jointed in base with an exclusively topographic criterion, resulting the following groups: muscles of the back, of the neck, of the thorax and of the pelvic member. The muscles associated to the thoracic waist are tried as common muscles of the member, without taking into account its insert neither its inervation. The homotipia criteria among both waists are established in this work, and standards to homologate the muscles that join the thoracic members and pelvics with the axial form are proposed. The classification in extrinsic or intrinsic in base to embriologic origin, its distal insert and its inervation is appealed for this purpose

Thorax (insect anatomy)

10.4067/s0716-98681998000100010

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Citations (2)