Beáta Sperlágh

Hungarian Academy of Sciences | HAS · Department of Pharmacology

Background and Purpose Tetrabenazine (TBZ), used for treating hyperkinetic disorders, inhibits vesicular monoamine transporter‐2 (VMAT‐2), which sequesters monoamines into vesicles for exocytosis. However, our knowledge of the effect of TBZ on monoaminergic transmission is limited. Herein, we provide neurochemical evidence regarding the effect of V...

Purinergic dysfunctions are associated with mania and depression pathogenesis. P2X7 receptor (P2X7R) mediates the IL-1β maturation via NLRP3 inflammasome activation. We tested in a mouse model of the subchronic amphetamine (AMPH)-induced hyperactivity whether P2X7R inhibition alleviated mania-like behavior through IL-1β. Treatment with JNJ-47965567...

Background Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of the receptor in O2 sensing and signal transduction is unknown. Methods The pres...

Both early childhood traumatic experiences and current stress increase the risk of suicidal behaviour, in which immune activation might play a role. Previous research suggests an association between mood disorders and P2RX7 gene encoding P2X7 receptors, which stimulate neuroinflammation. We investigated the effect of P2RX7 variation in interaction...

Background: As a member of the purinergic receptor family, divalent cation-regulated ionotropic P2X7 (P2rx7) plays a role in the pathophysiology of psychiatric disorders. This study aimed to investigate whether the effects of acute zinc administration and long-term zinc deprivation on depression-like behaviors in mice are mediated by P2X7 receptors...

ATP-gated P2X7 receptors (P2X7Rs) play a crucial role in brain disorders. However, how they affect normal and pathological synaptic transmission is still largely unclear. Here, by using whole-cell patch-clamp technique to record AMPA- and NMDA receptor-mediated excitatory postsynaptic currents (s/mEPSCs) in dentate gyrus granule cells (DG GCs), we...

Emotional stress is a leading risk factor in the development of neuropsychiatric disorders possibly via immune activation. P2X7 receptors promote neuroinflammation, and research suggests a relationship between chromosome region 12q2431, in which the P2X7R gene is located, and development of mood disorders, however, few studies concentrate on its as...

At high levels, extracellular ATP operates as a "danger" molecule under pathological conditions through purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Its endogenous activation is associated with neurodevelopmental disorders; however, its function during early embryonic stages remains largely unclear. Our objective was to det...

Phenylephrine (PE) is a canonical α 1 -adrenoceptor-selective agonist. However, unexpected effects of PE have been observed in preclinical and clinical studies, that cannot be easily explained by its actions on α 1 -adrenoceptors. The probability of the involvement of α 2 - and β-adrenoceptors in the effect of PE has been raised. In addition, our e...

P2X7 receptors regulate different aspects of neuronal development, including neurogenesis, dendritic outgrowth, and axonal elongation. Primary neuronal culture is a widely used model system in neuroscience as it enables to study molecular and cellular events caused by the activation of different ion channels, receptors, and transporters under contr...

Background: Immunological markers and related signaling molecules in the blood are altered in schizophrenia mouse models, in acutely relapsed patients with schizophrenia, and in persons at a clinically high risk for subsequently developing psychosis, highlighting their potential as prognostic and theranostic biomarkers. Therefore, we herein aimed...

Oxidative stress (OS) has been implicated in the progression of multiple neuropsychiatric disorders, including schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder, and autism. However, whether glial purinergic signaling interaction with oxidative/antioxidative system displays an important role in neuropsychiatric disorders is stil...

Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with...

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition caused by interactions of environmental and genetic factors. Recently we showed that activation of the purinergic P2X7 receptors is necessary and sufficient to convert maternal immune activation (MIA) to ASD-like features in male offspring mice. Our aim was to further substant...

Schizophrenia is a common psychiatric disorder which affects approximately 1% of the population worldwide. However, the complexity of etiology, treatment resistance and side effects induced by current antipsychotics, relapse prevention, and psychosocial rehabilitation are still to be uncovered. Caffeine, as the world's most widely consumed psychoac...

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative condition; characterized with the degeneration of the nigrostriatal dopaminergic pathway and neuroinflammation. During PD progression, microglia, the resident immune cells in the central nervous system (CNS) display altered activity, but their role in maintaining PD development ha...

Abstract Neuronal networks cause changes in behaviorally important information processing through the vesicular release of neurotransmitters governed by the rate and timing of action potentials (APs). Herein, we provide evidence that dopamine (DA), nonquantally released from the cytoplasm, may exert similar effects in vivo. In mouse slice preparati...

Background and Purpose P2Y12 receptors regulate different forms of pain and inflammation. In this study, we investigated the participation of P2Y12 receptors in an animal model of migraine. Experimental Approach We tested the effect of the centrally administered selective P2Y12 antagonist PSB‐0739 and P2Y12 receptor gene (P2ry12‐/‐) deficiency in...

The P2X purinoceptor 7 (P2RX7) mediates inflammatory microglial responses and is implicated in neuroimmune mechanisms of depression and neurodegenerative disorders. A number of studies suggest that psychosocial stress may precipitate depression through immune activation. Genetic association studies of P2RX7 variants with depression have been inconc...

Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoce...

Microglia, the main immunocompetent cells of the brain regulate neuronal function in health and disease, but their contribution to cerebral blood flow (CBF) remained elusive. Here we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. We show that microglia establish direct purinergic cont...

Parkinson's disease (PD) is a chronic, progressive neurodegenerative condition; characterized with the degeneration of the nigrostriatal dopaminergic pathway and neuroinflammation. During PD progression, microglia, the resident immune cells in the central nervous system (CNS) display altered activity, but their role in maintaining PD development ha...

Background: It has been consistently reported that the deficiency of the adenosine triphosphate (ATP) sensitive purinergic receptor P2X7 (P2X7R) ameliorates symptoms in animal models of brain diseases. Objective: This study aimed to investigate the role of P2X7R in rodent models of acute and subchronic schizophrenia based on phencyclidine (PCP) del...

During adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, we found that neurogenesis was disrupted...

The release of [³H]dopamine ([³H]DA) and [³H]noradrenaline ([³H]NA) in acutely perfused rat striatal and cortical slice preparations was measured at 37 °C and 17 °C under ischemic conditions. The ischemia was simulated by the removal of oxygen and glucose from the Krebs solution. At 37 °C, resting release rates in response to ischemia were increase...

Microglia take control Changes in the activity of microglia, the primary immune cells of the central nervous system, are linked with major human diseases, including stroke, epilepsy, psychiatric disorders, and neurodegeneration. Cserép et al. identified a specialized morphofunctional communication site between microglial processes and neuronal cell...

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by progressive loss of dopaminergic neurons that results in characteristic motor and non-motor symptoms. l-3,4 dihydroxyphenylalanine (l-DOPA) is the gold standard therapy for the treatment of PD. However, long-term use of l-DOPA leads to side effects such...

During adult hippocampal neurogenesis, the majority of newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of their intracellular contents. Here, we propose that phagocytosis is not merely a passive process of corpse removal but has an active role in maintaining adult hippocampal neurogenesis....

The purinergic signaling system, including P2 receptors, plays an important role in various central nervous system (CNS) disorders. Over the last few decades, a substantial amount of accumulated data suggest that most P2 receptor subtypes (P2X1, 2, 3, 4, 6, and 7, and P2Y 1 , 2 , 6 , 12 , and 13 ) regulate neuronal/neuroglial developmental processe...

Maternal immune activation (MIA) is a principal environmental risk factor contributing to autism spectrum disorder (ASD), which compromises fetal brain development at critical periods of pregnancy and might be causally linked to ASD symptoms. We report that endogenous activation of the purinergic ion channel P2X7 (P2rx7) is necessary and sufficient...

Microglia are the main resident immune-competent cell type of the central nervous system (CNS); these cells are highly sensitive to subtle changes in the chemical environment of the brain. Microglia are activated during diverse conditions, such as apoptosis, trauma, inflammation, and infection. The specific activities of microglia result from the c...

Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain’s immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-est...

The originally published version of this article contained an error in the name of the author Flóra Gölöncsér, which was incorrectly given as Flóra Göröncsér. This has now been corrected in both the PDF and HTML versions of the article.

Serotonergic mechanisms hosted by raphe nuclei have important roles in affiliative and agonistic behaviours but the separate roles of the two nuclei are poorly understood. Here we studied the roles of the dorsal (DR) and median raphe region (MRR) in aggression by optogenetically stimulating the two nuclei. Mice received three 3 min-long stimulation...

The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia comm...

Two subclasses of acid-sensing ion channels (ASIC3) and of ATP-sensitive P2X receptors (P2X3Rs) show a partially overlapping expression in sensory neurons. Here we report that both recombinant and native receptors interact with each other in multiple ways. Current measurements with the patch-clamp technique prove that ASIC3 stimulation strongly inh...

Maternal immune activation is a principal environmental risk factor contributing to neurodevelopmental psychiatric disorders, including autism spectrum disorder (ASD). Maternal infection is associated with the later emergence of ASD compromising foetal brain developmentat critical periods of pregnancy, and the elevation of maternal pro-inflammatory...

Thyroid hormone (TH) is present in the systemic circulation and thus should affect all cells similarly in the body. However, tissues have a complex machinery that allows tissue-specific optimization of local TH action that calls for the assessment of TH action in a tissue-specific manner. Here we report the creation of a Thyroid Hormone Action Indi...

Serotonergic and glutamatergic neurons of median raphe region (MRR) play a pivotal role in the modulation of affective and cognitive functions. These neurons synapse both onto themselves and remote cortical areas. P2X7 receptors (P2rx7) are ligand gated ion channels expressed by central presynaptic excitatory nerve terminals and involved in the reg...

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted e...

Representative video of the locomotion on day 1. Video shows one representative example from the stimulation control (see methods; this is a case of no stimulation) and another from the central stimulation group (see methods; intermittent stimulation at 50Hz theta burst frequency). (AVI)

Behavioral effects of intermittent 50Hz theta bursts and continuous 20Hz stimulation. (a) Time course of exploration and ambulation shown in time-bins representing the stimulation and non-stimulation periods of intermittent stimulation at 50Hz theta burst frequency. (b) Exploration and ambulation in mice submitted to continuous 20Hz stimulation in...

Representative pictures of the periaqueductal gray after c-Fos immunohistochemistry. Pictures were taken around -4.36 mm from the Bregma. Scalebar is 100μm. Group1: home cage controls; Group2: no ChR2 controls (transferred for 5 min to the conditioning cage, no ChR2 expression); Group3: no light controls (cage transfer, robust ChR2 expression, not...

Behavior in control groups was not different from that seen in intact mice. The scale of Y-axes is similar to those used for experimental groups (see Figs 1 and 3). (a) No rhythmic changes in exploration or ambulation were observed. Note that the scoring of behavior was time-structured in all groups as for effective intermittent stimulations (as in...

Representative pictures of the locomotion on day 1. Track visualization of the distance travelled during the fear conditioning. Higher velocity is indicated by bright color (yellow), slower movements or rest is signed by dark red (a,b). Heat maps represent the average time spent (s) at each location (c,d), blue meaning less time and red marking the...

Raw data of the experiment. File contains all data underlying the findings described in the manuscript and grouped by the number of the figures. (XLS)

Mitochondrial dysfunction, oxidative stress and their interplay are core pathological features of Parkinson’s disease. In dopaminergic neurons, monoamines and their metabolites provide an additional source of reactive free radicals during their breakdown by monoamine oxidase or auto-oxidation. Moreover, mitochondrial dysfunction and oxidative stres...

P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In...

Rationale Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. Objectives Here, we investigated the brain mechanisms underlying this phenomenon in rats. Methods The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, whi...

Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Usin...