Astrocytic P2X7 receptor regulates depressive-like behavioral reactions of mice in response to acute stressful stimulation.

Acute stress causes depressive-like reactions in the tail suspension (TST) and forced swim tests (FST) of mice. Similarly, inescapable foot shock is able to promote the development of anhedonia as indicated by decreased sucrose consumption of treated mice in the sucrose preference test (SPT). The astrocyte-specific deletion of the P2X7R by a conditional knockout strategy or its knockdown by the intracerebroventricular (i.

Astrocyte activation in hindlimb somatosensory cortex contributes to electroacupuncture analgesia in acid-induced pain.

Background: Several studies have confirmed the direct relationship between extracellular acidification and the occurrence of pain. As an effective pain management approach, the mechanism of electroacupuncture (EA) treatment of acidification-induced pain is not fully understood. The purpose of this study was to assess the analgesic effect of EA in this type of pain and to explore the underlying mechanism(s).

Airflow rates and breathlessness recovery from submaximal exercise in healthy adults: prospective, randomised, cross-over study.

Objectives: Facial airflow from a hand-held fan may reduce breathlessness severity and hasten postexertion recovery. Data from randomised controlled trials are limited and the optimal airflow speed remains unknown. We aimed to determine the effect of different airflow speeds on recovery from exercise-induced breathlessness.

Beneficial effect of electroacupuncture on the distribution of foreign substances in the brain of rats developing depression-like behavior.

We used low and high molecular weight fluorescence tracers to investigate the entry of foreign solutes into the brain parenchyma and their exit from it by the glymphatic system, during experimentally induced depressive-like behavior in rats. The tail suspension test (TST), as an acute stressor, is known to induce such a type of behavior, considered to model the human major depressive disorder (MDD). Electroacupuncture (EAP) relieves both depressive-like behavior in rodents and the symptoms of MDD in humans.

P2X7 receptor-mediated depression-like reactions arising in the mouse medial prefrontal cortex.

Major depressive disorder is a frequent and debilitating psychiatric disease. We have shown in some of the acute animal models of major depressive disorder (tail suspension test and forced swim test) that depression-like behavior can be aggravated in mice by the microinjection into the medial prefrontal cortex of the P2X7R agonistic adenosine 5'-triphosphate or its structural analog dibenzoyl-ATP, and these effects can be reversed by the P2X7R antagonistic JNJ-47965567. When measuring tail suspension test, the prolongation of immobility time by the P2YR agonist adenosine 5'-[β-thio]diphosphate and the reduction of the adenosine 5'-(γ-thio)triphosphate effect by P2Y1R (MRS 2179) or P2Y12R (PSB 0739) antagonists, but not by JNJ-47965567, all suggest the involvement of P2YRs.

ATP indirectly stimulates hippocampal CA1 and CA3 pyramidal neurons the activation of neighboring P2X7 receptor-bearing astrocytes and NG2 glial cells, respectively.

There is ongoing dispute on the question whether CNS neurons possess ATP-sensitive P2X7 receptors (Rs) or whether only non-neuronal cells bear this receptor-type and indirectly signal to the neighboring neurons. We genetically deleted P2X7Rs specifically in astrocytes, oligodendrocytes and microglia, and then recorded current responses in neurons to the prototypic agonist of this receptor, dibenzoyl-ATP (Bz-ATP). These experiments were made in brain slice preparations taken from the indicated variants of the P2X7R KO animals.

A Possible Causal Involvement of Neuroinflammatory, Purinergic P2X7 Receptors in Psychiatric Disorders.

P2X7 receptors (Rs) are prominent members of the P2XR family, which after binding ATP, open non-selective cationic channels, thereby allowing the transmembrane passage of Na+, Ca, and K+. Long-lasting and repetitive stimulation of the receptor by its agonist leads to the formation of large membrane pores permeable for organic cations of up to 900 Da molecular size. These pores are believed to play a role in apoptosis and inflammation.

Surgeon case volume and 5 years survival rate for colorectal cancer.

Aim: Many factors that influence patient outcome in colorectal surgery are not editable, and these are related either the tumor, the patient and the treatment. The surgeon- and hospital-related factors are independent predictors of outcome for colorectal cancer surgery and these are supervision, teaching/training, specialization in colorectal surgery, high caseload, high hospital caseload.

Materials Of Study: We evaluated the impact of the experience of 4 surgeons on the 5 years survival rate of patients with colon and rectal cancer and we valued if the surgeons' experience plays an equal role in both.

Inherent P2X7 Receptors Regulate Macrophage Functions during Inflammatory Diseases.

Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na, Ca, K).

Increasing Efficiency of Repetitive Electroacupuncture on Purine- and Acid-Induced Pain During a Three-Week Treatment Schedule.

Acupuncture (AP) is an important constituent of the therapeutic repertoire of traditional Chinese medicine and has been widely used to alleviate chronic painful conditions all over the world. We studied in rats the efficiency of electroacupuncture (EAP) applied to the Zusanli acupoint (ST36) as an analgesic treatment over a 3-week period of time on purine (α,β-methylene ATP, dibenzoyl-ATP)- and acid (pH 6.0 medium)-induced pain in the rat paw.

Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI.

Purpose: The purpose of this study was to create an algorithm that combines multiple machine-learning techniques to predict the expanded disability status scale (EDSS) score of patients with multiple sclerosis at two years solely based on age, sex and fluid attenuated inversion recovery (FLAIR) MRI data.

Materials And Methods: Our algorithm combined several complementary predictors: a pure deep learning predictor based on a convolutional neural network (CNN) that learns from the images, as well as classical machine-learning predictors based on random forest regressors and manifold learning trained using the location of lesion load with respect to white matter tracts. The aggregation of the predictors was done through a weighted average taking into account prediction errors for different EDSS ranges.

Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS.

Microglial cells, the resident macrophages of the central nervous system (CNS), exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell-damaging factors, they get transformed into an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species, and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them.

The P2X7 receptor: a new therapeutic target in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative illness with genetic risk as an etiological factor in a subset of cases. In AD with autosomal dominant inheritance, the extracellular β-amyloid (Aβ) aggregates and intracellular neurofibrillary tangles which consist of hyperphosphorylated tau, appear to be involved in the neuronal damage; however, other forms of AD may have a polygenetic causality. Microglial cells orchestrate pathophysiological events responsible for neuronal damage in AD.

P2X receptors and acupuncture analgesia.

Purinergic signaling has recently been suggested to constitute the cellular mechanism underlying acupuncture-induced analgesia (AA). By extending the original hypothesis on endogenous opioids being released during AA, Geoffrey Burnstock and Maiken Nedergaard supplied evidence for the involvement of purinoceptors (P2 and P1/A1 receptors) in the beneficial effects of AA. In view of certain pain states (e.

Author Correction: The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel.

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.

The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel.

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 inhibits the P2X3R current partly by a Ca-dependent mechanism.

Neuronal P2X7 Receptors Revisited: Do They Really Exist?

P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein-protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling the transition from the nonselective ion channel mode to a membrane pore allowing the passage of large molecules.

Primary gastrointestinal stromal tumour of the ileum pre-operatively diagnosed as an abdominal abscess.

The present case report described the acute presentation, diagnosis and management of a primary gastrointestinal stromal tumour (GIST) of the ileum. A male patient (age, 51 years) was admitted to Maggiore Hospital (Parma, Italy) due to presenting with fever, dysuria and lower abdominal pain. Ultrasonography and computed tomography showed a 7,5×5,5-cm pelvic mass containing air and purulent fluid indicative of an intraperitoneal abscess.

Acupuncture-Induced Analgesia: A Neurobiological Basis in Purinergic Signaling.

Chronic pain is a debilitating and rather common health problem. The present shortage in analgesic drugs with a favorable spectrum but without remarkable side effects furthered the search for alternative therapeutic manipulations. Increasing evidence from both basic and clinical research on acupuncture, a main alternative therapy of traditional Chinese medicine, suggests that chronic pain is sensitive to acupuncture procedures.