Alberto Perez-Samartin

Universidad del País Vasco / Euskal Herriko Unibertsitatea | UPV/EHU · Departamento de Neurociencias

Directional locomotion is a fundamental characteristic of many cells with great relevance in essential physiological and human pathological processes. For decades, research efforts have focused on studying specific individual processes and their corresponding biomolecular components involved in cellular locomotion movements. However, the notion tha...

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an e...

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an e...

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these le...

Multiple sclerosis (MS) affects almost 3 million people globally who suffer demyelination as a series of relapses and remissions that tend towards progressive deterioration over time. The proximate cause is auto-immune attack by the adaptive immune system; therapies directed against this are effective during the relapsing-remitting phase but are le...

Cannabidiol (CBD), the main non-psychoactive cannabinoid found in the cannabis plant, elicits several pharmacological effects via the 5-HT 1A receptor. The dorsal raphe nucleus (DRN) is the main serotonergic cluster in the brain that expresses the 5-HT 1A receptor. To date, the effect of CBD on the neuronal activity of DRN 5-HT cells and its intera...

The loss of functional capacity of the upper and lower extremities is one of the most common sequelae after a stroke, which affects the quality of life, generating situations of dependency. Functional electrical stimulation (FES) is one of the options for treating hand dexterity after stroke. The aim of this study was to review the published random...

The most common sequela after a stroke is the loss of arm function, and functional electrical stimulation (FES), is one of the options for treating it. Although FES has traditionally been used in isolation, different studies have shown that it can be used concomitantly with other neurorehabilitation techniques, enhancing the effects of therapy. The...

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promi...

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promi...

Shortage of oxygen and nutrients in the brain induces the release of glutamate and ATP that can cause excitotoxicity and contribute to neuronal and glial damage. Our understanding of the mechanisms of ATP release and toxicity in cerebrovascular diseases is incomplete. This review aims at summarizing current knowledge about the participation of key...

For a wide range of cells, from bacteria to mammals, locomotion movements are a crucial systemic behavior for cellular life. Despite its importance in a plethora of fundamental physiological processes and human pathologies, how unicellular organisms efficiently regulate their locomotion system is an unresolved question. Here, to understand the dyna...

Associative memory is the main type of learning by which complex organisms endowed with evolved nervous systems respond efficiently to certain environmental stimuli. It has been found in different multicellular species, from cephalopods to humans, but never in individual cells. Here we describe a motility pattern consistent with associative conditi...

Differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs) is a key event for axonal myelination in the central nervous system (CNS). Several growth factors and neurotransmitters like GABA are postulated as important regulators of that process, and different protein kinases may also participate in OL differentiatio...

Resumen La evidencia científica determina la validez en todas las intervenciones de salud. Estudios anteriores han demostrado la existencia de evidencia científica favorable en acupuntura. Actualmente, por sesgo de opinión o por desinformación, se intenta clasificar a la acupuntura como una seudociencia. Este estudio se justifica por la necesidad d...

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α/β-Hydrolase domain-containing 6 (ABHD6) contributes to the hydrolysis of the major endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS) and in the periphery. ABHD6 blockade has been proposed as novel strategy to treat multiple sclerosis (MS), based on the observation that the inhibitor WWL70 exerts protective anti-inf...

Microglia survey the brain microenvironment for signals of injury or infection and are essential for the initiation and resolution of pathogen- or tissue damage-induced inflammation. Understanding the mechanism of microglia responses during pathology is hence vital to promote regenerative responses. Here, we analyzed the role of purinergic receptor...

Associative memory is the main type of learning wherein complex organisms endowed with evolved nervous systems respond efficiently to determined environmental stimuli. This fundamental cognitive property has been evidenced in different multicellular species, from cephalopods to Humans, but never in individual cells. Here, following Pavlov’s experim...

Inwardly rectifying K⁺ (Kir) channel expression signals at an advanced stage of maturation during oligodendroglial differentiation. Knocking down their expression halts the generation of myelin and produces severe abnormalities in the central nervous system. Kir4.1 is the main subunit involved in the tetrameric structure of Kir channels in glial ce...

Resumen La estimulación de puntos o áreas en la calota craneana (craneopuntura) ha mostrado tener potentes efectos terapéuticos, sobre todo en patologías neurológicas. Estas técnicas, desarrolladas sobre todo a partir de 1950, no tienen un número suficiente de publicaciones científicas que apoyen una mayor aplicación en pacientes. Conceptualmente,...

Overactivation of purinergic receptors during cerebral ischemia results in a massive release of neurotransmitters, including adenosine triphosphate (ATP), to the extracellular space which leads to cell death. Some hypothetical pathways of ATP release are large ion channels, such as calcium homeostasis modulator 1 (CALHM1), a membrane ion channel th...

How motile, free unicellular organisms maximize the rate at which they encounter resources and develop optimal search strategies remains largely unknown. In fact, cell foraging is a very complex activity in which unicellular organisms integrate a diversity of external cues and develop efficient systemic movements to localize nourishment. These fora...

Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epi...

Entre los diferentes mecanismos biológicos que justifican los efectos analgésicos de la acupuntura, el del sistema purinérgico está tomando especial interés en los últimos años y, en concreto, por la activación de los receptores de adenosina tipo A1. En diferentes modelos experimentales en animales y en humanos se ha mostrado que la activación de l...

Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficientl...

[This corrects the article DOI: 10.1371/journal.pbio.1002466.].

Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA recep...

Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficientl...

El efecto placebo es un factor de sesgo en la interpretación de los resultados de cualquier intervención terapéutica que complica aún más la valoración de la eficacia de la acupuntura en estudios controlados aleatorizados. Desde el establecimiento del documento de consenso del NIH (National Institutes of Health) hay un impulso de homogeneizar estos...

En la última década son cada vez más frecuentes las referencias del uso de equipos de estimulación láser de puntos de acupuntura. Numerosas casas comerciales ofrecen aparatos de láser que tienen diversidad de características y su comparación es difícil. El objetivo de esta breve revisión es dilucidar si hay elementos de juicio para llegar a la conv...

Myelination requires oligodendrocyte-neuron communication, and both neurotransmitters and contact interactions are essential for this process. Oligodendrocytes are endowed with neurotransmitter receptors whose expression levels and properties may change during myelination. However, only scant information is availble about the extent and timing of t...

Unicellular organisms are open metabolic systems that need to process information about their external environment in order to survive. In most types of tissues and organisms, cells use calcium signaling to carry information from the extracellular side of the plasma membrane to the different metabolic targets of their internal medium. This informat...

Se sabe que la estimulación mediante acupuntura del punto E 36 (Zusanli) produce efectos beneficiosos en patologías inflamatorias tanto del tracto digestivo como del resto del cuerpo a través de unos mecanismos no del todo bien conocidos. La estimulación de E 36 (Zusanli) es capaz de reducir citocinas proinflamatorias. Por otra parte, la estimulaci...

The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced...

The endocannabinoids 2-araquidonoylglycerol (2-AG) and anandamide (AEA) are bioactive lipids crucially involved in the regulation of brain function in basal and pathological conditions. Blockade of endocannabinoid metabolism has emerged as a promising therapeutic strategy for inflammatory diseases of the central nervous system, including myelin dis...

Electrical stimulation of the E 36 (Zusanli) acupuncture point has shown beneficial effects for several inflammatory pathologies throughout the body and in the digestive system in particular. However, the mechanisms underlying this phenomenon are not well understood. Stimulation of E 36 (Zusanli) can result in a reduction in the level of proinflamm...

Besides a typical energetic molecule, adenosine triphosphate (ATP) acts also as neurotransmitter in the nervous system. ATP can be degraded by ectonucleotidases to adenosine and inosine. The mechanical stimulation of the acupuncture needle in muscular or subcutaneous tissues promotes the release of ATP and other purines which produces an antinocice...

Adenosine 5'-triphosphate (ATP) is released as a genuine co-transmitter, or as a principal purinergic neurotransmitter, in an exocytotic and non-exocytotic manner. It activates ionotropic (P2X) and metabotropic (P2Y) receptors which mediate a plethora of functions in the brain. In particular, P2X7 receptor (P2X7R) are expressed in all brain cells a...

During brain ischemia, an excessive release of glutamate triggers neuronal death through the overactivation of NMDA receptors (NMDARs); however, the underlying pathways that alter glutamate homeostasis and whether synaptic or extrasynaptic sites are responsible for excess glutamate remain controversial. Here, we monitored ischemia-gated currents in...

Adenosine receptor activation is involved in myelination and in apoptotic pathways linked to neurodegenerative diseases. In this study, we investigated the effects of adenosine receptor activation in the viability of oligodendrocytes of the rat optic nerve. Selective activation of A3 receptors in pure cultures of oligodendrocytes caused concentrati...

Pannexin1 (Panx1) is a plasma membrane channel permeable to relatively large molecules, such as ATP. In the central nervous system (CNS) Panx1 is found in neurons and glia and in the immune system in macrophages and T-cells. We tested the hypothesis that Panx1-mediated ATP release contributes to expression of Experimental Autoimmune Encephalomyelit...

Functional magnetic resonance imaging is an extraordinarily powerful research tool, because it allows measurement of brain activity in vivo, with high spatial and temporal resolution. However, its use is subject to many methodological restrictions. Several authors have proposed “criteria” in order to minimize the disparity of the results obtained....

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation. The Fmr1 knockout model recapitulates the main traits of the...

Acupuncture channels are entities which have been reported since antiquity. Nevertheless, the demonstration of their existence has become one of the most controversial research topics in Traditional Chinese Medicine. Although the data are not conclusive, there is strong evidence which indicates that cutaneous regions in which the acupuncture channe...

Overactivation of subtype P2X7 receptors can induce excitotoxic neuronal death by calcium (Ca(2+)) overload. In this study, we characterize the functional properties of P2X7 receptors using electrophysiology and Ca(2+) monitoring in primary cortical neuron cultures and in brain slices. Both electrical responses and Ca(2+) influx induced by ATP and...

The ancient texts of Traditional Chinese Medicine (TCM) show that the acupuncture points (APs) are located precisely and that the accuracy in their findings as well as their adequate manipulation are necessary for an achievement of a therapeutic effect. A lot of effort has been made in order to show the existence of the APs and, among them, the mea...

Oligodendrocytes, the myelinating cells of the CNS, are highly vulnerable to glutamate excitotoxicity, a mechanism involved in tissue damage in multiple sclerosis. Thus, understanding oligodendrocyte death at the molecular level is important to develop new therapeutic approaches to treat the disease. Here, using microarray analysis and quantitative...

Oligodendrocytes are highly vulnerable to glutamate excitotoxicity, a mechanism involved in tissue damage in multiple sclerosis. Thus, understanding oligodendrocyte death at the molecular level is important to develop new therapeutic approaches to treat that disease. Here, using microarray analysis and quantitative PCR, we observed that Dusp6 phosp...

Oligodendrocytes, the myelinating cells of the CNS, are highly vulnerable to glutamate excitotoxicity, a mechanism involved in tissue damage in multiple sclerosis. Thus, understanding oligodendrocyte death at the molecular level is important to develop new therapeutic approaches to treat the disease. Here, using microarray analysis and quantitative...

Parameters of the dissipative metabolic network. MSb: the number of metabolic subsystems; Reg. Sign. Coef.: Coefficient values of the regulatory signals; Flux Parameter 1°: integration function parameters belonging to the first flux of the subsystems; Flux Parameter 2°: integration function parameters belonging to the second flux of the subsystems;...

Different studies have shown that cellular enzymatic activities are able to self-organize spontaneously, forming a metabolic core of reactive processes that remain active under different growth conditions while the rest of the molecular catalytic reactions exhibit structural plasticity. This global cellular metabolic structure appears to be an intr...

Amyloid beta (Abeta) oligomers accumulate in brain tissue of Alzheimer disease patients and are related to pathogenesis. The precise mechanisms by which Abeta oligomers cause neurotoxicity remain unresolved. In this study, we investigated the role of ionotropic glutamate receptors on the intracellular Ca2+ overload caused by Abeta. Using rat cortic...

Brain ischemia leading to stroke is a major cause of disability in developed countries. Therapeutic strategies have most commonly focused on protecting neurons from ischemic damage. However, ischemic damage to white matter causes oligodendrocyte death, myelin disruption, and axon dysfunction, and it is partially mediated by glutamate excitotoxicity...

Using western blottings, microdialysis, and functional assays we tested the hypothesis that phencyclidine (PCP) modifies the expression and function of glutamate (Glu) transporters in the rat frontal cortex. Western blotting studies revealed that administration of PCP (10 mg/kg/day; 7 days) increased significantly the expression of the astrocytic G...

Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using "metabolic networks models" are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used "dissipative metabolic networks"...

Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis (MS). Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X(7) purinergic receptors expressed by these cells. Sustained activation of P2X(7) receptors in vivo causes lesions that are reminiscent of the major featu...

Glutamate kills neurons by excitotoxicity, which is caused by sustained activation of glutamate receptors. In recent years, it has been shown that glutamate can also be toxic to white matter oligodendrocytes and to myelin by this mechanism. In particular, glutamate receptor-mediated injury to these cells can be triggered by activation of alpha-amin...

Glutamate excitotoxicity and complement attack have both been implicated separately in the generation of tissue damage in multiple sclerosis and in its animal model, experimental autoimmune encephalomyelitis. Here, we investigated whether glutamate receptor activation sensitizes oligodendrocytes to complement attack. We found that a brief incubatio...

We have analyzed the presence of persistence properties in rabbit brain electrical signals by means of non-equilibrium statistical physics tools. To measure long-memory properties of these experimental signals, we have first determined whether the data are fractional Gaussian noise (fGn) or fractional Brownian motion (fBm) by calculating the slope...

Glutamate uptake is crucial to terminate glutamate signaling and to prevent excitotoxicity. The present study describes the expression of functional glutamate transporters GLAST and GLT-1 in oligodendrocytes by means of electrophysiology, uptake assays, and immunocytochemistry. Inhibition of glutamate uptake, both in oligodendrocyte cultures and in...

Excitotoxic oligodendroglial death is one of the mechanisms which has been proposed to underlie demyelinating diseases of the CNS. We describe here functional consequences of excitotoxic lesions to the rabbit optic nerve by studying the visual evoked potentials (VEPs) measured in the visual cortex. Nerves were slowly infused with the excitotoxin ka...

We show here that clozapine, a beneficial antipsychotic, down-regulates the expression of the glutamate transporter GLT-1 in the rat cerebral cortex, thereby reducing glutamate transport and raising extracellular glutamate levels. Clozapine treatment (25--35 mg kg(-1) day(-1) orally) reduced GLT-1 immunoreactivity in several brain regions after 3 w...

Oligodendrocytes, the myelinating cells of CNS axons, are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes. Receptors in these cells are commonly activated by glutamate that is released from axons and glial cells. In addition, oligodendrocytes contribute to the control of extracellular glutama...

Osmolarity-dependent ionic currents from follicle-enclosed Xenopus oocytes (follicles) were studied using electrophysiological techniques. Whole follicle currents were monitored using a two-electrode voltage clamp and single-channel activity was measured using the patch-clamp technique. In follicles held at -60 mV two chloride currents were activat...

The superior colliculus (SC) is a laminar structure which can be separated into superficial and deep layers according to morphological and functional criteria. The superficial layers are interconnected with many nuclei, most of which process visual information. Also, these layers are known to project to the pontine grey. The topography of the proje...

The mammalian superior colliculus (SC) may be divided into distinct layers on the basis of cytoarchitectonic criteria. These layers have different functions and patterns of connectivity. The superficial layers (stratum zonale, stratum griseum superficiale (SGS) and stratum opticum) are intimately associated with the processing of visual information...

The neuronal projection between the superficial layers of the mammalian superior colliculus (SC) and the ipsilateral dorsal lateral geniculate nucleus (dLGN) is well established. However, the participation of the contralateral SC remains controversial. In this study we have presented evidence for the existence of SC neurons which project to the con...

The aim of this study is to describe the morphological features of the origin cells of the visual corticopontine projection in the cat. To this end, the pontine grey matter of adult cats was injected with Rhodamine Latex Microspheres. The resulting, retrogradely marked cells of the visual cortex, were subsequently injected intracellularly with Luci...

Injections of the low diffusion retrograde tracer rhodamine latex microspheres were made in the pontine grey matter of the cat in order to study the cortical convergence to the pons. We found a different distribution of cells in the convex surface of the brain hemisphere making ventral or dorsolateral injections. In the first case, cells were group...

In the method described, the head of a fixed-stage microscope and the attached micromanipulator are simultaneously displaced during focussing movements of the microscope. This design allows axial displacements of the microscope towards the cell to be injected. This arrangement makes the filling of neurons in brain slices by intracellular iontophore...