The role of maternal infections in neurodevelopmental psychiatric disorders: focus on the P2X7/NLRP3/IL-1β signalling pathway.

Immune activation in the prenatal and early postnatal periods is increasingly implicated in the aetiology of neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia, by disrupting critical neurodevelopmental processes. The impact of immune activation on brain development can be influenced by the type, timing, location, and severity of the infection. Viral, bacterial, and parasitic infections, as well as maternal autoimmune diseases, can lead to the activation of the purinergic P2X7 receptors, thereby contributing to neuroinflammation.

Targeting P2X7 mitigates neurobehavioural alterations in a mouse model of post-acute sequelae of SARS-CoV-2 infection.

The COVID-19 pandemic has imposed a significant global health burden, leading to various long-term consequences, including persistent neuropsychiatric symptoms in a substantial proportion of infected individuals. This study investigates the role of the purinergic receptor P2X7 in mediating behaviour changes in a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC). We show that infection with a mouse-adapted SARS-CoV-2 strain induces anxiety- and depression-like behaviours in male mice, associated with elevated P2X7 receptor expression in the prefrontal cortex and hippocampus, as well as increased IFN-γ levels in the striatum.

From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression.

Early-life stress may increase the risk of neuropsychiatric disorders via immune activation. While the purinergic signaling pathway is implicated in psychiatric disorders, the specific role of the P2X7 receptor (P2X7R) in anxiety, depression, and childhood trauma still requires further clarification. Upon chronic stress, excessive ATP release activates purinergic P2X7R signalling in the brain contributing to long-lasting neuroinflammation, which potentially promotes the development of psychiatric disorders.

Distinct expression of NEAT1 isoforms in Parkinson's disease models suggests different roles of the variants during the disease course.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Recently long non-coding RNAs (lncRNAs) have emerged as possible molecular hubs in the diverse pathomechanisms of the disease. Among them, NEAT1 gained particular interest due to findings suggesting both protective and deleterious effects of this lncRNA in PD models.

P2X7 receptor inhibition alleviates mania-like behavior independently of interleukin-1β.

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.

Blood oxygen regulation via P2Y12R expressed in the carotid body.

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 O sensing and signal transduction is unknown.

Methods: The presence of P2Y12R was established by immunoblotting, RT qPCR and immunohistochemistry.

The antidepressant effect of short- and long-term zinc exposition is partly mediated by P2X7 receptors in male mice.

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. The antidepressant-like effect of elevated zinc level was studied using a single acute intraperitoneal injection in C57BL6/J wild-type and P2rx7 gene-deficient (P2rx7 -/-) young adult and elderly animals in the tail suspension test (TST) and the forced swim test (FST).

P2X7 purinergic receptor modulates dentate gyrus excitatory neurotransmission and alleviates schizophrenia-like symptoms in mouse.

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 revealed a modulation by P2X7Rs of presynaptic sites, especially originated from entorhinal cortex (EC)-GC path but not the mossy cell (MC)-GC path.

Variation along P2RX7 interacts with early traumas on severity of anxiety suggesting a role for neuroinflammation.

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 association with anxiety. Our aim was to investigate the effects of P2RX7 variation in interaction with early childhood traumas and recent stressors on anxiety.

P2 receptor-mediated signaling in the physiological and pathological brain: From development to aging and disease.

The purinergic pathway mediates both pro-inflammatory and anti-inflammatory responses, whereas the breakdown of adenosine triphosphate (ATP) is in a critical equilibrium. Under physiological conditions, extracellular ATP is maintained at a nanomolar concentration. Whether released into the medium following tissue damage, inflammation, or hypoxia, ATP is considered a clear indicator of cell damage and a marker of pathological conditions.

The Pharmacological Effects of Phenylephrine are Indirect, Mediated by Noradrenaline Release from the Cytoplasm.

Phenylephrine (PE) is a canonical α-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-adrenoceptors. The probability of the involvement of α- and β-adrenoceptors in the effect of PE has been raised.

Analysis of P2X7-Induced Neuronal Branching.

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 controlled conditions. Primary neuronal cultures derived from normal and genetically modified mouse models can be used with a wide array of molecular biological, anatomical, and functional techniques such as RNA sequencing, western blots, immunostaining, Ca imaging, and electrophysiology.

Glial Purinergic Signaling-Mediated Oxidative Stress (GPOS) in Neuropsychiatric Disorders.

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 still unclear. In this review, we firstly summarize the oxidative/antioxidative pathways shared in different glial cells and highlight the cell type-specific difference in response to OS.

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions.

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 cells in the neurovascular unit that shape CBF in both mice and humans.

The dualistic role of the purinergic P2Y12-receptor in an in vivo model of Parkinson's disease: Signalling pathway and novel therapeutic targets.

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 has remained unclear to date. The purinergic P2Y-receptor (P2YR), which is expressed on the microglia in the CNS has been shown to regulate microglial activity and responses; however, the function of the P2YR in PD is unknown.

Contribution of analog signaling to neurotransmitter interactions and behavior: Role of transporter-mediated nonquantal dopamine release.

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 preparations, (+/-)-3,4-methylenedioxy-methamphetamine (MDMA, or ecstasy) and β-phenylethylamine (β-PEA)-induced DA release in the striatum and nucleus accumbens (NAc), two regions of the brain involved in reward-driven and social behavior and inhibited the axonal stimulation-induced release of tritiated acetylcholine ([ H]ACh) in the striatum.

Caffeine consumption and schizophrenia: A highlight on adenosine receptor-independent mechanisms.

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 psychoactive drug, plays a crucial role in daily life.

Pharmacogenetic excitation of the median raphe region affects social and depressive-like behavior and core body temperature in male mice.

Aims: Median raphe region (MRR) is an important bottom-up regulatory center for various behaviors as well as vegetative functions, but detailed descriptions and links between the two are still largely unexplored.

Methods: Pharmacogenetics was used to study the role of MRR in social (sociability, social interaction, resident intruder test) and emotional behavior (forced swim test) parallel with some vegetative changes (biotelemetry: core body temperature). Additionally, to validate pharmacogenetics, the effect of clozapine-N-oxide (CNO), the ligand of the artificial receptor, was studied by measuring (i) serum and brainstem concentrations of CNO and clozapine; (ii) MRR stimulation induced neurotransmitter release in hippocampus; (iii) CNO induced changes in body temperature and locomotor activity.

Involvement of P2Y receptors in a nitroglycerin-induced model of migraine in male mice.

Background And Purpose: P2Y receptors regulate different forms of pain and inflammation. In this study, we investigated the participation of P2Y receptors in an animal model of migraine.

Experimental Approach: We tested the effect of the centrally administered selective P2Y antagonist PSB-0739 and P2Y receptor gene (P2ry12 ) deficiency in acute nitroglycerin-treated mice.