The absence of P2X7 receptors (P2rx7) on non-haematopoietic cells leads to selective alteration in mood-related behaviour with dysregulated gene expression and stress reactivity in mice
Open accessAbstract
The purpose of this study was to explore how genetic deletion and pharmacological antagonism of the P2X7 receptor (P2rx7) alter mood-related behaviour, gene expression and stress reactivity in the brain. The forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperlocomotion (AH) tests were used in wild-type (P2rx7+/+) and P2rx7-deficient (P2rx7−/−) mice. Biogenic amine levels were analysed in the amygdala and striatum, adrenocorticotropic hormone (ACTH) and corticosterone levels were measured in the plasma and pituitary after restraint stress. Chimeric mice were generated by bone marrow transplantation. A whole genome microarray analysis with real-time polymerase chain reaction validation was performed on the amygdala. In the absence of P2rx7s decreased behavioural despair in the FST, reduced immobility in the TST and attenuated amphetamine-induced hyperactivity were detected. Basal norepinephrine levels were elevated in the amygdala, whereas stress-induced ACTH and corticosterone responses were alleviated in P2rx7−/− mice. Sub-acute treatment with the selective P2rx7 antagonist, Brilliant Blue G, reproduced the effect of genetic deletion in the TST and AH test in P2rx7+/+ but not P2rx7−/− mice. No change in behavioural phenotype was observed in chimeras lacking the P2rx7 in their haematopoietic compartment. Whole genome microarray analysis indicated a widespread up- and down-regulation of genes crucial for synaptic function and neuroplasticity by genetic deletion. Here, we present evidence that the absence of P2rx7s on non-haematopoietic cells leads to a mood-stabilizing phenotype in several behavioural models and suggest a therapeutic potential of P2rx7 antagonists for the treatment of mood disorders.
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Gene knockout or pharmacological inhibition of P2X7 receptors induced antidepressant-like behavior in mice exposed to stress, accompanied by HPA axis restoration.
“Noteworthy, gene knockout or pharmacological inhibition of P2X7 receptors induced antidepressant-like behavior in mice exposed to stress, accompanied by HPA axis restoration [163, 164].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [164]
Treatment with P2X7R antagonists induces antidepressant-like effects in various animal models.
“Evidence from pharmacological studies have further corroborated this hypothesis, since treatment with P2X7R antagonists induce antidepressant-like effects in various animal models.”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [85]
Data from P2X7R knockout mice indicate that absence of the P2X7R results in increased resilience to stress and a phenotype showing less depression-like characteristics.
“Altogether, data from P2X7R KO mice indicates that absence of the P2X7R results in increased resilience to stress, and a phenotype showing less depression-like characteristics.”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [85]
P2X7R knockout mice present reduced immobility time in both the forced swim test and the tail suspension test.
“Additional studies further corroborated these initial findings, with observations that P2X7R KO mice presents reduced immobility time in both the FST [85] and the TST [20,85].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [85]
Both pharmacological and genetic evidence strongly suggest that P2X7R stimulation during stress increases vulnerability and subsequent development of behavioral adversities associated with the neurobiology of depression.
“Altogether, both pharmacological and genetic evidence strongly suggest that P2X7R stimulation during stress increase the vulnerability and subsequent development of behavioral adversities associated with the neurobiology of depression (Table 2).”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [85]
Brilliant Blue G decreased the immobility time of mice exposed to the tail suspension test.
“and decreased the immobility time of mice exposed to TST [85].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [85]
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BackgroundP2X7 receptors in the nervous system
Sperlágh, B., Vizi, E. S., Wirkner, K., & Illés, P. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.03.007 · Cited by 374 · cited 5× · see citing works
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BackgroundThe P2X 7 purinergic receptor: from physiology to neurological disorders
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“In line with previous data (Basso et al. 2009), P2rx7x/x mice spent significantly less time with immobility (i.”
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MethodPurinergic signalling in inflammation of the central nervous system
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“Accordingly, P2rx7s are involved in the regulation of different aspects of the hostdefence reaction (Chen & Brosnan, 2006 ; di Virgilio et al. 2009).”
BackgroundEmerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons
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“2006) : (1) its intracellular carboxyl-terminal domain is longer than those of other P2X receptor subunits ; (2) it has several splice variants that display different functionality in P2rx7+/+ and knockout mice lines (Nicke et al. 2009) ; (3) its persistent activation elicits the opening of a membrane pore permeable to”
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“…have revealed that non-synonymous single nucleotide polymorphisms in the human P2X7 gene (P2RX7) affect receptor function (Roger et al. 2010; Stokes et al. 2010) and are associated with bipolar disorder (Barden et al. 2006; Hejjas et al. 2009; McQuillin et al. 2009; Nagy et al. 2008;…”
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“…et al. 2003), the differential expression of glutamate receptor subunits in bipolar and major depressive disorders (Meador-Woodruff et al. 2001; Toro & Deakin, 2005), the antidepressant properties of glutamate receptor antagonists and modulators (Sanacora et al. 2008) and the regulation of…”
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“Gene polymorphism studies have revealed that non-synonymous single nucleotide polymorphisms in the human P2X7 gene (P2RX7) affect receptor function (Roger et al. 2010; Stokes et al. 2010) and are associated with bipolar disorder (Barden et al. 2006; Hejjas et al. 2009; McQuillin et al. 2009; Nagy…”
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“This treatment elicited the significant change of 570 transcripts with >2FC, which is comparable to the gene expression changes found by others in the brain after systemic endotoxin treatment (Marques et al. 2009; Marsh et al. 2009; Mastronardi et al. 2007; Perreau et al. 2007).”
ResultJakus, Z., Simon, E., Frommhold, D., Sperandio, M., & Mócsai, A. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081859 · Cited by 119 · cited 2× · see citing works
“1 allele as described previously (Jakus et al. 2009).”
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“These observations confirm and extend previous data, which showed decreased immobility in the TST (Basso et al. 2009) and decreased floating time in the FST on the second day (Boucher et al. 2011) after genetic deletion.”
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“These include abnormalities in the level of glutamate (Hashimoto et al. 2007), genetic polymorphisms (Mundo et al. 2003), the differential expression of glutamate receptor subunits in bipolar and major depressive disorders (Meador-Woodruff et al. 2001; Toro & Deakin, 2005), the antidepressant…”
BackgroundLack of ATP-evoked GABA and glutamate release in the hippocampus of P2X7 receptor-/- mice
Papp, L., Vizi, E. S., & Sperlágh, B. (2004) · Neuroreport · doi:10.1097/00001756-200410250-00017 · Cited by 102 · cited 2× · see citing works
“The activation of P2rx7s elicits Ca2+ influx (Miras-Portugal et al. 2003), followed by increased glutamate and subsequent c-aminobutyric acid (GABA) release (Alloisio et al. 2008; Papp et al. 2004; Patti et al. 2006; Sperlagh et al. 2002).”
BackgroundResultAssociation between depression and the Gln460Arg polymorphism of P2RX7 gene: A dimensional approach
Hejjas, K., Szekely, A., Domotor, E., Halmai, Z., Balogh, G., Schilling, B., Sarosi, A., Faludi, G., Sasvari‐Szekely, M., & Nemoda, Z. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30799 · Cited by 100 · cited 2× · see citing works
“2010) and are associated with bipolar disorder (Barden et al. 2006; Hejjas et al. 2009; McQuillin et al. 2009; Nagy et al. 2008; Soronen et al. 2011) and major depressive disorder (Lucae et al.”
BackgroundPurinergic modulation of microglial cell activation
Sperlágh, B., & Illés, P. (2006) · Purinergic Signalling · doi:10.1007/s11302-006-9043-x · Cited by 99 · cited 11× · see citing works
“Systemic LPS administration (250 mg/ kg i.p.) caused a significant elevation in IL-1b levels (83.94¡3.01 pg/ml, n=8, F1,28=45.2, p 0.001, Fig.”
BackgroundInfluentialSelf-citationP2X7 Receptors in Rat Brain: Presence in Synaptic Terminals and Granule Cells
Miras‐Portugal, M. T., Dı́az-Hernández, M., Giráldez, L., Hervás, C., Gómez‐Villafuertes, R., Pérez‐Sen, R., Gualix, J., & Pintor, J. J. (2003) · Neurochemical Research · doi:10.1023/a:1025690913206 · Cited by 98 · cited 2× · see citing works
“The activation of P2rx7s elicits Ca2+ influx (Miras-Portugal et al. 2003), followed by increased glutamate and subsequent c-aminobutyric acid (GABA) release (Alloisio et al. 2008; Papp et al. 2004; Patti et al. 2006; Sperlagh et al. 2002).”
BackgroundP2X7 receptors on microglial cells mediate injury to cortical neurons in vitro
Skaper, S. D., Facci, L., Culbert, A. A., Evans, N. A., Chessell, I. P., Davis, J. B., & Richardson, J. C. (2006) · Glia · doi:10.1002/glia.20379 · Cited by 94 · see citing works
Soronen, P., Mantere, O., Melartin, T. K., Suominen, K. H., Vuorilehto, M. S., Rytsälä, H. J., Arvilommi, P., Holma, I. A. K., Holma, M., Jylhä, P. J., et al. (2011) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31179 · Cited by 91 · see citing works
A final common pathway for depression? Progress toward a general conceptual framework
Stone, E. A., Lin, Y., & Quartermain, D. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.08.007 · Cited by 82 · cited 1× · see citing works
“According to the current view, major depressive disorder and bipolar disorder are caused by plastic alterations of distributed networks involving multiple neurotransmitters and pathways (Stone et al. 2008).”
BackgroundRegulation of Immune Response by P2X7 Receptor
Chen, L., & Brosnan, C. F. (2006) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v26.i6.30 · Cited by 80 · cited 1× · see citing works
“Accordingly, P2rx7s are involved in the regulation of different aspects of the hostdefence reaction (Chen & Brosnan, 2006 ; di Virgilio et al. 2009).”
BackgroundEinat, H. (2006) · Behavior Genetics · doi:10.1007/s10519-006-9093-4 · Cited by 72 · cited 1× · see citing works
“As a behavioural model of manic pole of bipolar disorder (Einat, 2007), the AH test was used in our study.”
MethodP2RX7: A bipolar and unipolar disorder candidate susceptibility gene?
Green, E., Grozeva, D., Raybould, R., Elvidge, G. P., MacGregor, S., Craig, I., FARMER, A. E., McGuffin, P., Forty, L., Jones, L. A., et al. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30931 · Cited by 66 · cited 1× · see citing works
“…bipolar disorder (Barden et al. 2006; Hejjas et al. 2009; McQuillin et al. 2009; Nagy et al. 2008; Soronen et al. 2011) and major depressive disorder (Lucae et al. 2006; Soronen et al. 2011; but see Green et al. 2009; Grigoroiu-Serbanescu et al. 2010; Lavebratt et al. 2010; Viikki et al. 2011).”
BackgroundNowak, G., Legutko, B., Skolnick, P., & Popik, P. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)01589-6 · Cited by 61 · cited 2× · see citing works
“…disorders (Meador-Woodruff et al. 2001; Toro & Deakin, 2005), the antidepressant properties of glutamate receptor antagonists and modulators (Sanacora et al. 2008) and the regulation of glutamate receptor subunits by clinically used antidepressants (Nowak et al. 1998; Skolnick et al. 1996).”
BackgroundCastro, J. E., Varea, E., Márquez, C., Cordero, M. I., Poirier, G. L., & Sandi, C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008618 · Cited by 60 · cited 1× · see citing works
“Our findings also indicated P2rx7-dependent changes in monoamine levels in the amygdala, which is an intrinsic part of the neuronal circuitry regulating emotions and the site of action of antidepressants (Castro et al. 2010).”
BackgroundFunctional evidence for presynaptic P2X7 receptors in adult rat cerebrocortical nerve terminals
Alloisio, S., Cervetto, C., Passalacqua, M., Barbieri, R., Maura, G., Nobile, M., & Marcoli, M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.10.041 · Cited by 56 · cited 2× · see citing works
“2003), followed by increased glutamate and subsequent c-aminobutyric acid (GABA) release (Alloisio et al. 2008; Papp et al. 2004; Patti et al. 2006; Sperlagh et al. 2002).”
BackgroundP2 receptor-mediated modulation of neurotransmitter release—an update
Sperlágh, B., Heinrich, A., & Csölle, C. (2007) · Purinergic Signalling · doi:10.1007/s11302-007-9080-0 · Cited by 56 · cited 1× · see citing works
“The primary role of P2rx7s in the brain is the modulation of neurotransmitter release (Anderson & Nedergaard, 2006; Sperlagh et al. 2006, 2007a).”
BackgroundSelf-citationGrigoroiu‐Serbânescu, M., Herms, S., Mühleisen, T. W., Georgi, A., Diaconu, C. C., Strohmaier, J., Czerski, P. M., Hauser, J., Leszczyńska-Rodziewicz, A., Jamra, R. A., et al. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30952 · Cited by 55 · see citing works
Chromatographic analysis of dopamine metabolism in a Parkinsonian model
Baranyi, M., Milusheva, E., Vizi, E. S., & Sperlágh, B. (2006) · Journal of Chromatography A · doi:10.1016/j.chroma.2006.03.018 · Cited by 51 · cited 2× · see citing works
“Biogenic amines were measured by a liquid–liquid, two-dimensional reversed phase and ion pair-reversed phase chromatographic separation, as described earlier (Baranyi et al. 2006) using a Gilson liquid chromatographic system (Gilson Medical Electronics Inc.”
MethodSelf-citationP2RX7 Gln460Arg polymorphism is associated with depression among diabetic patients
Nagy, G., Rónai, Z., Somogyi, A., Sasvári‐Székely, M., Rahman, O. A., Máté, A., Varga, T., & Nemoda, Z. (2008) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.08.021 · Cited by 47 · cited 2× · see citing works
“2010) and are associated with bipolar disorder (Barden et al. 2006; Hejjas et al. 2009; McQuillin et al. 2009; Nagy et al. 2008; Soronen et al. 2011) and major depressive disorder (Lucae et al.”
BackgroundPatti, L., Raiteri, L., Grilli, M., Parodi, M., Raiteri, M., & Marchi, M. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.016 · Cited by 46 · cited 2× · see citing works
“The activation of P2rx7s elicits Ca2+ influx (Miras-Portugal et al. 2003), followed by increased glutamate and subsequent c-aminobutyric acid (GABA) release (Alloisio et al. 2008; Papp et al. 2004; Patti et al. 2006; Sperlagh et al. 2002).”
BackgroundResultZelena, D., Domokos, Á., Barna, I., Mergl, Z., Haller, J., & Makara, G. B. (2008) · Endocrinology · doi:10.1210/en.2007-1537 · Cited by 45 · cited 1× · see citing works
“Adrenocorticotropic hormone (ACTH) and corticosterone in the trunk blood and in acutely isolated pituitaries were measured by radioimmunoassay in 50-ml unextracted samples as described previously (Zelena et al. 2008).”
MethodSelf-citationViikki, M., Kampman, O., Anttila, S. A. K., Illi, A., Setälä-Soikkeli, E., Huuhka, M., Mononen, N., Lehtimäki, T. J., & Leinonen, E. V. J. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.02.023 · Cited by 44 · cited 2× · see citing works
“2011) and major depressive disorder (Lucae et al. 2006; Soronen et al. 2011; but see Green et al. 2009; Grigoroiu-Serbanescu et al. 2010; Lavebratt et al. 2010; Viikki et al. 2011).”
BackgroundCaspase 1 deficiency reduces inflammation-induced brain transcription
Mastronardi, C. A., Whelan, F., Yildiz, O. A., Hannestad, J. O., Elashoff, D. A., McCann, S. M., Licinio, J., & Wong, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701366104 · Cited by 42 · cited 1× · see citing works
“This treatment elicited the significant change of 570 transcripts with >2FC, which is comparable to the gene expression changes found by others in the brain after systemic endotoxin treatment (Marques et al. 2009; Marsh et al. 2009; Mastronardi et al. 2007; Perreau et al. 2007).”
ResultKaryotype and intermale aggression in wild house mice: Ecology and speciation
Capanna, E., Corti, M., Mainardi, D., Parmigiani, S., & Brain, P. F. (1984) · Behavior Genetics · doi:10.1007/bf01065541 · Cited by 40 · see citing works
Sanacora, G. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.003 · Cited by 39 · cited 1× · see citing works
“Consistent with the presumed dysfunction of glutamatergic transmission and consequent neuroplasticity changes in depression (Sanacora, 2010 ; Sanacora et al. 2008), a downregulation of different a-amino-3-hydroxyl-5-methyl4-isoxazole-propionate (AMPA) and metabotropic glutamate receptor subunits…”
BackgroundCsölle, C., & Sperlágh, B. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.11.011 · Cited by 36 · cited 1× · see citing works
“In contrast to rats, isolation does not increase but slightly decreases depressionlike behaviour in mice, at least in the Swiss strain of this species (Hilakivi et al. 1989).”
BackgroundSelf-citationCsölle, C., Heinrich, A., Kittel, Á., & Sperlágh, B. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05391.x · Cited by 29 · cited 1× · see citing works
“Adrenocorticotropic hormone (ACTH) and corticosterone in the trunk blood and in acutely isolated pituitaries were measured by radioimmunoassay in 50-ml unextracted samples as described previously (Zelena et al. 2008).”
MethodSelf-citationTHE INTEGRITY OF THE SOCIAL HIERARCHY IN MICE FOLLOWING ADMINISTRATION OF PSYCHOTROPIC DRUGS
Poshivalov, V. P. (1980) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1980.tb08712.x · Cited by 23 · cited 1× · see citing works
“Mice establish strong dominance hierarchies in both their natural habitats and the laboratory (Capanna et al. 1984; Ferrari et al. 1998; Poshivalov 1980).”
BackgroundGene interactions in depression: pathways out of darkness
Harvey, M., Belleau, P., & Barden, N. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.08.011 · Cited by 23 · cited 1× · see citing works
“These mutations might underlie the susceptibility to genetically related mood disorders (Harvey et al. 2007; Sluyter et al. 2010).”
BackgroundATP‐induced [Ca2+]i changes and depolarization in GH3 cells
Chung, H. S., Park, K., Cha, S. K., et al. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703253 · Cited by 22 · cited 1× · see citing works
“Functional P2rx7s are expressed on pituitary cells (Chung et al. 2000), which, together with our in vitro results, suggests a direct ATP effect on ACTH secretion.”
BackgroundMelatonin treatment in old mice enables a more youthful response to LPS in the brain
Perreau, V. M., Bondy, S. C., Cotman, C. W., Sharman, K., & Sharman, E. H. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.09.005 · Cited by 19 · cited 1× · see citing works
“This treatment elicited the significant change of 570 transcripts with >2FC, which is comparable to the gene expression changes found by others in the brain after systemic endotoxin treatment (Marques et al. 2009; Marsh et al. 2009; Mastronardi et al. 2007; Perreau et al. 2007).”
ResultMilusheva, E., Baranyi, M., Kormos, E., Hracskó, Z., Vizi, E. S., & Sperlágh, B. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.11.017 · Cited by 18 · cited 1× · see citing works
“[3H]Dopamine release experiments [3H]Dopamine release experiments on acute striatal slices were performed according to the method described in Milusheva et al. (2010).”
MethodSelf-citationFunctional significance of P2RX7 polymorphisms associated with affective mood disorders
Sluyter, R., Stokes, L., Fuller, S. J., Skarratt, K. K., Gu, B. J., & Wiley, J. S. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.04.013 · Cited by 17 · cited 1× · see citing works
“These mutations might underlie the susceptibility to genetically related mood disorders (Harvey et al. 2007; Sluyter et al. 2010).”
Background
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P2X7 receptor: an emerging target in central nervous system diseases
Sperlágh, B., & Illes, P. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.08.002 · Cited by 390 · see citing works
Self-citationIwata, M., Ota, K. T., Li, X.-Y., Sakaue, F., Li, N., Dutheil, S., Banasr, M., Duric, V., Yamanashi, T., Kaneko, K., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.11.026 · Cited by 387 · see citing works
“This finding is consistent with a report that a nonselective P2X7R antagonist decreases immobility in the FST only after repeated testing (59).”
Update of P2X receptor properties and their pharmacology: IUPHAR Review 30
Illés, P., Müller, C. E., Jacobson, K. A., Grütter, T., Nicke, A., Fountain, S. J., Kennedy, C., Schmalzing, G., Jarvis, M. F., Stojilković, S. S., et al. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15299 · Cited by 315 · see citing works
“The beneficial effects of BBB-permeable P2X7 receptor antagonists in AD animal models also support the notion of pathological microglial activation in AD (Csölle et al., 2013).”
BackgroundP2X7 Receptors: Channels, Pores and More
Volonté, C., Apolloni, S., Skaper, S. D., & Burnstock, G. (2012) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152712803581137 · Cited by 254 · see citing works
“[154] Gene Deletion”
BackgroundThe microglial ATP‐gated ion channel P2X7 as a CNS drug target
Bhattacharya, A., & Biber, K. (2016) · Glia · doi:10.1002/glia.23001 · Cited by 221 · see citing works
“…in a model of sucrose consumption that is reflective of hedonic behavior, pharmacological antagonism of P2X7 (by AZ-10606120 and A-804598) restored the deficit observed in drinking sucrosewater (anhedonia) either under chronic stress or by systemic administration of LPS (Csolle et al., 2013b).”
BackgroundInfluentialBhattacharya, A., Wang, Q., Ao, H., Shoblock, J. R., Lord, B., Aluisio, L. E., Fraser, I. C., Nepomuceno, D. H., Neff, R. A., Welty, N., et al. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12314 · Cited by 200 · see citing works
“This is however, in contrast to protective effects of despair behaviour in P2X7 knockout mice in the forced swim test on day 1, observed by other groups (Basso et al., 2009; Csolle et al., 2013).”
BackgroundResultInfluentialThe P2X7 Receptor: Central Hub of Brain Diseases
Andrejew, R., Oliveira-Giacomelli, Á., Ribeiro, D. E., Glaser, T., Arnaud-Sampaio, V. F., Lameu, C., & Ulrich, H. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00124 · Cited by 162 · see citing works
Ullrich (2018) · doi:10.1038/mp.2017.188 · Cited by 145 · see citing works
Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology
Ribeiro, D. E., Oliveira-Giacomelli, Á., Glaser, T., Arnaud-Sampaio, V. F., Andrejew, R., Dieckmann, L., Baranova, J., Lameu, C., Ratajczak, M. Z., & Ulrich, H. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00965-3 · Cited by 145 · see citing works
Role of neuro-immunological factors in the pathophysiology of mood disorders
Bhattacharya, A., Derecki, N. C., Lovenberg, T. W., & Drevets, W. C. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4214-0 · Cited by 149 · see citing works
“Likewise, minocycline also attenuated LPS-induced behavioral changes and markers of neuroinflammation in mice (Henry et al. 2008).”
BackgroundInfluentialP2X7 Receptor Signaling in Stress and Depression
Ribeiro, D. E., Roncalho, A. L., Glaser, T., Ulrich, H., Wegener, G., & Joca, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112778 · Cited by 129 · see citing works
“Sci. 2019, 20, 2778 12 of 26 like decreased sucrose preference, reduced social interaction ratio and high immobility time in the FST [150].”
BackgroundResultInfluentialCsölle, C., Baranyi, M., Zsilla, G., Kittel, Á., Gölöncsér, F., Illes, P., Papp, E., Vizi, E. S., & Sperlágh, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066547 · Cited by 128 · see citing works
“Under basal conditions, we detected a dysregulation of monoaminergic transmission, and these results are consistent with our previous findings in the amygdala [25].”
BackgroundResultInfluentialSelf-citationRecent advances in CNS P2X7 physiology and pharmacology: Focus on neuropsychiatric disorders
Bhattacharya, A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00030 · Cited by 115 · see citing works
“…hypothesis, in a model of sucrose consumption that is reflective of hedonic behavior, pharmacological antagonism of P2X7 restored the deficit observed in drinking sucrosewater (anhedonia) either under chronic stress or by systemic administration of lipopolysaccharides (LPS) (Csolle et al., 2013b).”
BackgroundInfluentialP2X and P2Y Receptors—Role in the Pathophysiology of the Nervous System
Puchałowicz, K., Tarnowski, M., Baranowska‐Bosiacka, I., Chlubek, D., & Dziedziejko, V. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151223672 · Cited by 109 · see citing works
“[49] contradict the role attributed to IL-1β derived from haematopoietic cells, such as monocytes or microglia, as a factor responsible for mood disorders depending on P2X7, although they do not exclude the participation of other nervous tissue cells, e.”
BackgroundPurinergic mechanisms in neuroinflammation: An update from molecules to behavior
Beamer, E. H., Gölöncsér, F., Horváth, G., Bekő, K., Otrokocsi, L., Koványi, B., & Sperlágh, B. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.09.019 · Cited by 103 · see citing works
“Acute stress induced depressiveelike behaviors, following LPS challenge are also alleviated by P2X7 receptor antagonism, (Csolle et al., 2013b; Ma et al., 2014).”
BackgroundInfluentialSelf-citationP2X7 Receptor: A Potential Therapeutic Target for Depression?
Deussing, J. M., & Arzt, E. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.07.005 · Cited by 97 · see citing works
Purinergic receptors in psychiatric disorders
Krügel, U. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.032 · Cited by 95 · see citing works
“In agreement, the treatment with LPS evoked less IL1β in the amygdala in P2X7 receptor knockout than in wildtype mice (Csölle et al., 2013a).”
P2X7 receptor antagonists: a patent review (2010–2015)
Park, J.-H., & Kim, Y. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1246538 · Cited by 92 · see citing works
“Moreover, P2X7R knockout (KO) mice in models of depression and mania demonstrated protective roles, and P2X7R antagonists such as AZ10606120 and A804598 showed antidepressant profiles [24,25].”
BackgroundFarooq, R. K., Tanti, A., Ainouche, S., Roger, S., Belzung, C., & Camus, V. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.07.016 · Cited by 83 · see citing works
Bhattacharya, A., Lord, B., Grigoleit, J., He, Y., Fraser, I. C., Campbell, S. N., Taylor, N., Aluisio, L. E., O’Connor, J. C., Papp, M., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0141-6 · Cited by 82 · see citing works
Regulation of P2X7 receptor expression and function in the brain
Jimenez-Mateos, E. M., Smith, J., Nicke, A., & Engel, T. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.12.008 · Cited by 79 · see citing works
Pathological ATPergic Signaling in Major Depression and Bipolar Disorder
Illés, P., Verkhratsky, A., & Tang, Y. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00331 · Cited by 77 · see citing works
Astrocytes and major depression: The purinergic avenue
Zhao, Y. F., Verkhratsky, A., Tang, Y. C., & Illés, P. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109252 · Cited by 73 · see citing works
Pharmacology of a Novel Central Nervous System–Penetrant P2X7 Antagonist JNJ-42253432
Lord, B., Aluisio, L. E., Shoblock, J. R., Neff, R. A., Varlinskaya, E. I., Ceusters, M., Lovenberg, T. W., Carruthers, N. I., Bonaventure, P., Letavic, M. A., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.218487 · Cited by 73 · see citing works
“This will be the third publication indicating a role of the P2X7 pathway in amphetamine hyperactivity (Bhattacharya et al., 2013; Csölle et al., 2013).”
BackgroundLetavic, M. A., Savall, B. M., Allison, B. D., Aluisio, L. E., Andrés, J. I., Angelis, M. D., Ao, H., Beauchamp, D. A., Bonaventure, P., Bryant, S., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00408 · Cited by 74 · see citing works
Recourt, K., de Boer, P., van der Ark, P. D., Beneš, H., van Gerven, J., Ceusters, M., Nueten, L. V., Drevets, W. C., Bhatacharya, A., Browning, M. D., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02557-5 · Cited by 69 · see citing works
“…P2X7 knockout mice demonstrated decreased dexamphetamine-induced hyperloco-motion and IL ‐ 1 β release in the brain [35, 36], and reduced depressive-like behaviors in the automated tail suspension test, forced swim test and post-stress sucrose preference test, compared with wild type mice [37, 38].”
Timmers, M., Ravenstijn, P. G. M., Xi, L., Triana‐Baltzer, G., Furey, M., Hemelryck, S. V., Biewenga, J., Ceusters, M., Bhattacharya, A., van den Boer, M., et al. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881118800067 · Cited by 69 · see citing works
P2X7 Antagonists as Potential Therapeutic Agents for the Treatment of CNS Disorders
Chrovian, C. C., Rech, J. C., Bhattacharya, A., & Letavic, M. A. (2014) · Progress in medicinal chemistry · doi:10.1016/b978-0-444-63380-4.00002-0 · Cited by 67 · see citing works
Interactions of neuroimmune signaling and glutamate plasticity in addiction
Gipson, C. D., Rawls, S. M., Scofield, M. D., Siemsen, B. M., Bondy, E. O., & Maher, E. E. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02072-8 · Cited by 67 · see citing works
“It is also worth mentioning that P2X7 receptor antagonism or genetic deletion reduces hyperactivity induced by amphetamines [35, 69, 118].”
BackgroundRole of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine
Gubert, C., Fries, G. R., Pfaffenseller, B., Ferrari, P., Coutinho‐Silva, R., Morrone, F. B., Kapczinski, F. P., & Battastini, A. M. O. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-9031-z · Cited by 64 · see citing works
“Our study is in agreement with earlier data that showed that the blockade/deletion of P2X7R abrogates AMPH-induced hyperactivity [17].”
BackgroundResultRecourt, K., van der Aart, J., Jacobs, G. E., de Kam, M., Drevets, W. C., Nueten, L. V., Kanhai, K. M. S., Siebenga, P. S., Zuiker, R. G. J. A., Ravenstijn, P. G. M., et al. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120914206 · Cited by 61 · see citing works
“P2X7 knockout mice also showed ameliorated depressive-like behaviours in the automated tail suspension test, repeated forced swim tests and sucrose preference test compared to wild-type mice (Boucher et al., 2011; Csölle et al., 2013b).”
MethodResultMetzger, M. W., Walser, S. M., Dedic, N., Aprile-Garcia, F., Jakubcakova, V., Adamczyk, M., Webb, K. J., Uhr, M., Refojo, D., Schmidt, M. V., et al. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3487-16.2017 · Cited by 59 · see citing works
“In addition, KO mice revealed P2X7R-dependent alterations in different aspects of emotional behavior related to mood disorders (Basso et al., 2009; Boucher et al., 2011; Csölle et al., 2013).”
BackgroundInfluentialUnderstanding the role of P2X7 in affective disorders—are glial cells the major players?
Stokes, L., Spencer, S. J., & Jenkins, T. A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00258 · Cited by 58 · see citing works
“Pharmacological blockade of P2X7 was also effective in altering depressive-like behavior and LPS-induced sickness behavior in mice (Csölle et al., 2013a,b).”
BackgroundMethodResultInfluentialA novel radioligand for the ATP-gated ion channel P2X7: [3H] JNJ-54232334
Lord, B., Ameriks, M. K., Wang, Q., Fourgeaud, L., Vliegen, M., Verluyten, W. L. M., Haspeslagh, P., Carruthers, N. I., Lovenberg, T. W., Bonaventure, P., et al. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.09.026 · Cited by 55 · see citing works
P2X7 receptors drive poly(I:C) induced autism-like behavior in mice
Horváth, G., Otrokocsi, L., Bekő, K., Baranyi, M., Kittel, Á., Fritz-Ruenes, P. A., & Sperlágh, B. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1895-18.2019 · Cited by 56 · see citing works
“…/ mice has been extensively analyzed in previous studies: altered stress reactivity, but no change in basal locomotor activity, was observed in different studies (Basso et al., 2009; Csölle et al., 2013b; Bartlett et al., 2014; Otrokocsi et al., 2017) in agreement with the present study (Fig.”
BackgroundResultSelf-citationMa, M., Ren, Q., Zhang, J.-C., & Hashimoto, K. (2014) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2014.12.1.31 · Cited by 55 · see citing works
The role of P2X7 receptors in a rodent PCP-induced schizophrenia model
Koványi, B., Csölle, C., Calovi, S., Hanuska, A., Kató, E., Köles, L., Bhattacharya, A., Haller, J., & Sperlágh, B. (2016) · Scientific Reports · doi:10.1038/srep36680 · Cited by 52 · see citing works
P2X7 Receptors Mediate Innate Phagocytosis by Human Neural Precursor Cells and Neuroblasts
Lovelace, M. D., Gu, B. J., Eamegdool, S. S., Weible, M. W., Wiley, J. S., Allen, D. G., & Chan‐Ling, T. (2014) · Stem Cells · doi:10.1002/stem.1864 · Cited by 51 · see citing works
P2X7 Receptors Drive Spine Synapse Plasticity in the Learned Helplessness Model of Depression
Otrokocsi, L., Kittel, Á., & Sperlágh, B. (2017) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx046 · Cited by 51 · see citing works
Self-citationSynthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X7 Antagonists
Letavic, M. A., Lord, B., Bischoff, F., Hawryluk, N. A., Pieters, S., Rech, J. C., Sales, Z. S., Velter, A. I., Ao, H., Bonaventure, P., et al. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml400040v · Cited by 51 · see citing works
Gölöncsér, F., & Sperlágh, B. (2014) · The Journal of Headache and Pain · doi:10.1186/1129-2377-15-24 · Cited by 49 · see citing works
“Selection of dose was based on previous studies [38,39].”
MethodSelf-citationThe P2X7 receptor: a new therapeutic target in Alzheimer’s disease
Illés, P., Rubini, P., Huang, L., & Tang, Y. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1575811 · Cited by 49 · see citing works
Gürsel (2018) · doi:10.1016/j.neubiorev.2018.02.005 · Cited by 47 · see citing works
“Conversely, ATP elicited glutamate release from mouse hippocampal slices that was largely prevented by P2X7-KO (Csolle et al., 2013b) and, while the cell type releasing glutamate was not established, astrocytes remain a strong candidate.”
BackgroundResultInfluentialRibeiro, D. E., Müller, H. K., Elfving, B., Eskelund, A., Joca, S. R., & Wegener, G. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119872173 · Cited by 45 · see citing works
Backlund, L., Lavebratt, C., Frisén, L., Nikamo, P., Sudic, D. H., Träskman‐Bendz, L., Landén, M., Edman, G., Vawter, M. P., Ösby, U., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043057 · Cited by 41 · see citing works
“Absence of P2rx7 in mouse brain have been shown to decrease depressive-like behavior and attenuate amphetamineinduced hyperactivity [46] whereas activation of the P2RX7 gene may lead to glutamate over-activation and secondary to depressive symptoms [47].”
Ion Channel Dysfunction and Neuroinflammation in Migraine and Depression
Eren‐Koçak, E., & Dalkara, T. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.777607 · Cited by 39 · see citing works
Purinergic neurone-glia signalling in cognitive-related pathologies
Illés, P., & Verkhratsky, A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.005 · Cited by 34 · see citing works
“…identified for the antidepressant phenotype of P2X7 -/- mice, such as absence of P2X7 receptor-mediated glutamate release, elevated basal brain-derived neurotrophic factor (BDNF) production, enhanced neurogenesis, and increased serotonin bioavailability in the hippocampus (Csolle et al., 2013).”
BackgroundRole of neuroglia in neuropathic pain and depression
Liu, Q., Li, R., Yang, W., Cui, R., & Li, B. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105957 · Cited by 35 · see citing works
Rudolph, D. A., Alcázar, J., Ameriks, M. K., Anton, A. B., Ao, H., Bonaventure, P., Carruthers, N. I., Chrovian, C. C., Angelis, M. D., Lord, B., et al. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.06.004 · Cited by 33 · see citing works
Brain immune cells characterization in UCMS exposed P2X7 knock-out mouse
Troubat, R., Leman, S., Pinchaud, K., Surget, A., Barone, P. R., Roger, S., Guisquet, A. L., Brizard, B., Belzung, C., & Camus, V. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.02.012 · Cited by 33 · see citing works
Kongsui, R., Beynon, S. B., Johnson, S. J., Mayhew, J., Kuter, P., Nilsson, M., & Walker, F. R. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.05.017 · Cited by 29 · see citing works
“…675 676 677 678 679 680 681 682 683 684 685 R. Kongsui et al. / Brain, Behavior, and Immunity xxx (2014) xxx–xxx 11 reporting that P2X7 knockout mice respond to acutely stressful situations with higher levels of behavioural resilience (Csolle et al., 2013; Basso et al., 2009; Boucher et al., 2011).”
BackgroundNieto-Quero, A., Chaves-Peña, P., Santín, L. J., Pérez‐Martín, M., & Pedraza, C. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100356 · Cited by 31 · see citing works
“The P2X7 receptor (P2X7R) is a member of the purinergic receptor family that plays a pivotal role in stress-induced inflammation (Koo and Duman, 2008, 2009a, 2009b) and may be involved in the modulation of essential mechanisms of stress responses, such as neurogenesis (Csölle et al., 2013).”
BackgroundParoxetine suppresses recombinant human P2X7 responses
Dao-Ung, P., Skarratt, K. K., Fuller, S. J., & Stokes, L. (2015) · Purinergic Signalling · doi:10.1007/s11302-015-9467-2 · Cited by 29 · see citing works
Animal Models for the Investigation of P2X7 Receptors
Sluyter, R., Adriouch, S., Fuller, S. J., Nicke, A., Sophocleous, R. A., & Watson, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098225 · Cited by 26 · see citing works
Unique genetic loci identified for emotional behavior in control and chronic stress conditions
Carhuatanta, K. A. K., Shea, C. J. A., Herman, J. P., & Jankord, R. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00341 · Cited by 26 · see citing works
Gölöncsér, F., Baranyi, M., Balázsfi, D., Demeter, K., Haller, J., Freund, T. F. F., Zelena, D., & Sperlágh, B. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00325 · Cited by 25 · see citing works
“P2rx7s have been shown to contribute to the pathophysiology of depression (Csolle et al., 2013a,b; Iwata et al., 2016; Otrokocsi et al., 2017), bipolar disorder (Csolle et al., 2013a; Lord et al., 2014) and schizophrenia (Kovanyi et al., 2016).”
BackgroundResultInfluentialChrovian, C. C., Soyode-Johnson, A., Ao, H., Bacani, G. M., Carruthers, N. I., Lord, B., Nguyen, L., Rech, J. C., Wang, Q., Bhattacharya, A., et al. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00303 · Cited by 25 · see citing works
Purinergic transmission in depressive disorders
Szopa, A., Socała, K., Serefko, A., Doboszewska, U., Wróbel, A., Poleszak, E., & Właź, P. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107821 · Cited by 25 · see citing works
Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor
Gil, B., Smith, J., Tang, Y., Illés, P., & Engel, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042380 · Cited by 26 · see citing works
Ribeiro, D. E., Casarotto, P. C., Staquini, L., Pinto e Silva, M. A., Biojone, C., Wegener, G., & Joca, S. (2019) · PeerJ · doi:10.7717/peerj.7834 · Cited by 21 · see citing works
“Similar to the clinical scenario, and contrary to usual protocols of FST and TST, the antidepressant-like effect on LH model is observed only after repeated pharmacological treatment, i.e., administration of classical antidepressant drugs during 7–21 days (Petty, Kramer & Wilson, 1992; Nankai et al., 1995; Mansbach, B…”
BackgroundMethodResultInfluentialP2X7 Receptor as a Potential Target for Major Depressive Disorder
Huang, Z., & Tan, S. (2021) · Current Drug Targets · doi:10.2174/1389450122666210120141908 · Cited by 20 · see citing works
P2X7 Receptor-Related Genetic Mouse Models – Tools for Translational Research in Psychiatry
Urbina-Treviño, L., von Mücke-Heim, I.-A., & Deussing, J. M. (2022) · Frontiers in Neural Circuits · doi:10.3389/fncir.2022.876304 · Cited by 22 · see citing works
Tang, Y., Illes, P., Zhang, Y., Yin, H.-Y., & Rubini, P. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220302152400 · Cited by 20 · see citing works
Substituted 5,6-(Dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)-methanones as P2X7 Antagonists
Ziff, J., Rudolph, D. A., Stenne, B., Koudriakova, T. B., Lord, B., Bonaventure, P., Lovenberg, T. W., Carruthers, N. I., Bhattacharya, A., Letavic, M. A., et al. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00304 · Cited by 20 · see citing works
The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression
Wang, K., Huang, S., Fu, D., Yang, X., Ma, L., Zhang, T., Zhao, W., Deng, D., Ding, Y., Zhang, Y., et al. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14536 · Cited by 19 · see citing works
The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder
Gonçalves, M. C. B., Andrejew, R., & Gubert, C. (2022) · CNS Drugs · doi:10.1007/s40263-022-00934-0 · Cited by 19 · see citing works
Purinergic signaling in cognitive impairment and neuropsychiatric symptoms of Alzheimer's disease
Ribeiro, D. E., Petiz, L. L., Glaser, T., Oliveira‐Giacomelli, Á., Andrejew, R., Saab, F. D. A. R., Milanis, M. D. S., Campos, H. C., Arnaud-Sampaio, V. F., de Oliveira, S. L. B., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109371 · Cited by 20 · see citing works
Illés, P., Rubini, P., Ulrich, H., Yin, H., & Tang, Y. C. (2025) · MedComm · doi:10.1002/mco2.70177 · Cited by 18 · see citing works
Lainiola, M., & Linden, A.-M. (2017) · Alcohol · doi:10.1016/j.alcohol.2017.06.002 · Cited by 18 · see citing works
Huang, H., Zheng, S., Chen, M., Xie, L., Li, Z., Guo, M. A., Wang, J., Lu, M., & Zhu, X. (2021) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2021.101993 · Cited by 18 · see citing works
Spyrka, J., & Hess, G. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.03.007 · Cited by 16 · see citing works
Potula, R., Gentile, T. A., Meissler, J. J., Shekarabi, A., Wiah, S., Farkas, D. J., Inan, S., Eisenstein, T. K., & Rawls, S. M. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.09.012 · Cited by 15 · see citing works
P2X7 Purinergic Receptor Is Involved in the Pathophysiology of Mania: a Preclinical Study
Gubert, C., Andrejew, R., Leite, C. E., Moritz, C. E. J., Scholl, J. N., Figueiró, F., Kapczinski, F. P., Magalhães, P. V. D. S., & Battastini, A. M. O. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01817-0 · Cited by 14 · see citing works
The effects of P2X7 receptor knockout on emotional conditions over the lifespan of mice
Gao, L., Lin, Z., Xie, G., Zhou, T. G., Hu, W., Liu, C., Liu, X., Wang, X., Qian, M., & Ni, B. (2018) · Neuroreport · doi:10.1097/wnr.0000000000001136 · Cited by 13 · see citing works
Bipolar disorder and 1513A>C P2RX7 polymorphism frequency
Gubert, C., Andrejew, R., Moritz, C. E. J., Dietrich, F., Vasconcelos-Moreno, M. P., Tietbohl-Santos, B., Fijtman, A., Kauer‐Sant’Anna, M., Kapczinski, F. P., Magalhães, P. V. D. S., et al. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.11.055 · Cited by 13 · see citing works
Purinergic modulation of glutamate transmission: An expanding role in stress-linked neuropathology
Mayhew, J., Graham, B. A., Biber, K. P. H., Nilsson, M., & Walker, F. R. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.06.023 · Cited by 13 · see citing works
P2X7 receptors are involved in stress-related behaviours and antidepressant effect
Ribeiro, D. E., Stanquini, L. A., Biojone, C., Casarotto, P. C., Elfving, B., Müller, H. K., Wegener, G., & Joca, S. R. L. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.11.350 · Cited by 11 · see citing works
Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors
Cherninskyi, A., Storozhuk, M., Maximyuk, O. P., Kulyk, V. B., & Krishtal, O. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00986-8 · Cited by 11 · see citing works
Gentile, T. A., Simmons, S. J., Tallarida, C. S., Su, S., Rom, S., Watson, M. N., Reitz, A. B., Potula, R., & Rawls, S. M. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.12.022 · Cited by 11 · see citing works
“In fact, the most relevant behavioral evidence is that P2X7 antagonism or genetic deletion reduces hyperactivity induced by amphetamines (Gubert et al., 2016; Bhattacharya et al., 2013; Csölle et al., 2013).”
BackgroundP2X7 receptor inhibition alleviates mania-like behavior independently of interleukin-1β
Gölöncsér, F., Baranyi, M., Tod, P., Maácz, F., & Sperlágh, B. (2024) · iScience · doi:10.1016/j.isci.2024.109284 · Cited by 9 · see citing works
“21 Others have shown that 7 days of AMPH treatment reduced 5-HT and glutamate levels in both hippocampal and striatal structures, but the use of non-selective P2X7R antagonist BBG did not alter this effect.”
BackgroundSelf-citationRen, X.-Y., Rubini, P., Engel, T., Tang, Y., & Illés, P. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107989 · Cited by 9 · see citing works
Cheng, X.-Y., Ren, W.-J., Li, X., Deussing, J. M., Illés, P., Tang, Y., & Rubini, P. (2024) · Purinergic Signalling · doi:10.1007/s11302-024-10047-6 · Cited by 8 · see citing works
“Unfortunately, our results oppose some of the previously reported ones and we cannot explain this discrepancy [18, 30].”
Targeting inflammasome complexes as a novel therapeutic strategy for mood disorders
de Miranda, A. S., Toscano, E. C. D. B., O’Connor, J. C., & Teixeira, A. L. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2366872 · Cited by 9 · see citing works
“Systemic or intracerebroventricular administration of the nonselective P2X7R antagonist BBG or the high-affinity and selective P2X7R antagonist, A438079, prevented D-amphetamine sulfate salt (AMPH)-induced manic-like behaviors in rodents [104,105,135].”
BackgroundNinjinyoeito exerts an antidepressant‐like effect by enhancing the central noradrenergic system
Tsutsumi, S., Watanabe, T., Hatae, A., Hirata, M., Omori, H., Taniguchi, C., Nagao, M., Kubota, K., Katsurabayashi, S., & Iwasaki, K. (2022) · Traditional & Kampo Medicine · doi:10.1002/tkm2.1306 · Cited by 8 · see citing works
“Consistent with these findings, decreased immobility time and increased NE levels in the amygdala were observed in mice with genetic deletion or pharmacological blockade of the P2X7 receptor [27].”
BackgroundSmith, K. L., Todd, S. M., Boucher, A. A., Bennett, M. R., & Arnold, J. C. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134575 · Cited by 7 · see citing works
Serotonergic neurons in the treatment of mood disorders: The dialogue with astrocytes
Charvériat, M., & Guiard, B. P. (2021) · Progress in brain research · doi:10.1016/bs.pbr.2021.01.006 · Cited by 7 · see citing works
P2X7 in Bipolar and Depressive Disorders
Barron, M. L., Werry, E. L., McGregor, I. S., & Kassiou, M. (2013) · Springer eBooks · doi:10.1007/978-3-642-40282-1_31 · Cited by 5 · see citing works
Iring-Varga, B., Baranyi, M., Gölöncsér, F., Tod, P., & Sperlágh, B. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1241406 · Cited by 4 · see citing works
Self-citationvon Mücke-Heim, I.-A., Oldekamp, J., Metzger, M. W., Kläffgen, S., Tang, H., Walser, S. M., Dedic, N., Rammes, G., Holsboer, F., Wurst, W., et al. (2025) · Purinergic Signalling · doi:10.1007/s11302-025-10074-x · Cited by 4 · see citing works
“While CSDS had no effect on FST behaviour, other studies have demonstrated that repeated or prolonged FST protocols resulted in decreased immobility in KO compared to WT mice [67, 78].”
Kristóf, Z., Szabó, D., Sperlágh, B., Török, D., & Gonda, X. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104687 · Cited by 5 · see citing works
“In animal studies, P2RX7 KO-mice produced a controversial relationship with anxiety-like behaviour [21,135–137], with no consensus on its role.”
Self-citationMethodological guidelines for P2X receptor assays and data interpretation
Górecki, D. C., Adinolfi, E., Adriouch, S., Coutinho‐Silva, R., Engel, T., Gölöncsér, F., Haag, F., Illés, P., Jacobson, K. A., Koch‐Nolte, F., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08730-0 · Cited by 3 · see citing works
“Furthermore, detailed reporting of environmental conditions, such as housing, circadian phase of testing, and prior handling, is critical, as P2XR activity can be in fl uenced by stress, immune state, and metabolic factors [223, 224].”
Self-citationZhao, M., Xing, L., Li, Y., Zhang, J., Liu, Y., Ye, F., & Chen, S. (2025) · Poultry Science · doi:10.1016/j.psj.2025.105192 · Cited by 3 · see citing works
Autocrine activation of P2X7 receptors mediates catecholamine secretion in chromaffin cells
Maldifassi, M. C., Guerra‐Fernández, M. J., Ponce, D., Alfonso‐Bueno, S., Maripillán, J., Vielma, A. H., Báez‐Matus, X., Marengo, F. D., Acuña‐Castillo, C., Sáez, J. C., et al. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16371 · Cited by 3 · see citing works
“…gene might also change the expression of other receptors and channels involved in Ca 2 + dynamics, as it has been observed in the amygdala of the P2X7 receptor (cid:4) / (cid:4) mouse, where, among others, α 2 adrenoceptors and dopamine D 2 receptors were downregulated (Csölle et al., 2013).”
BackgroundPurinergic P2X Receptors as Therapeutic Targets
Stokes, L., Bidula, S. M., & Sluyter, R. (2024) · Springer eBooks · doi:10.1007/978-3-031-52197-3_13 · Cited by 2 · see citing works
Emerging Microglial Therapies and Targets in Clinical Trial
Yan, L., & Crotti, A. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_35 · Cited by 2 · see citing works
Abstracts from the 2017 Italian-German Purine Club Meeting
Dettori, I., Coppi, E., Fusco, I., Cencetti, F., Gaviano, L., Bruni, P., Colotta, V., Catarzi, D., Pedata, F., & Pugliese, A. M. (2017) · Purinergic Signalling · doi:10.1007/s11302-017-9581-4 · Cited by 2 · see citing works
The Role of ATP and P2X Purinoceptor 7 in the Development of Cerebral Tau
Gao, A. F. (2018) · TSpace (University of Toronto) · Cited by 1 · see citing works
Ribeiro, D. E., Müller, H. K., Elfving, B., Joca, S. R. L., & Wegener, G. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/395194
乳癌抑制遺伝子BRCA1の機能解析 : CDK2-BRCA1-NPM pathway(第105回日本外科学会定期学術集会)
太田, 智., 呉, 文., 速水, 亮., 佐藤, 工., & 福田, 護. (2005) · 日本外科学会雑誌
- Authors
- Csölle, C., Andó, R. D., Kittel, Á., Gölöncsér, F., Baranyi, M., Soproni, K., Zelena, D., Haller, J., Németh, T., Mócsai, A., & Sperlágh, B.
- Affiliations
- Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences (IEM HAS), Budapest, Hungary
- HUN-REN Institute of Experimental Medicine (HU)
- Semmelweis University (HU)
- Corresponding author
- Sperlágh, Beáta
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-01
- Volume
- 16
- Issue
- 1
- Pages
- 213-233
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC3666310
- OpenAlex
- W2102853311
- Semantic Scholar
- 6b74d60ae26da2b868b16b175ff8521099b8edeb
- Cited by
- 108
- References
- 80
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 5 · 2019: 13 · 2018: 13 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 4 · 2012: 2
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- Wellcome Trust (087782)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- P2X7 receptor, depression-like behavior, anxiety-like behavior, stress reactivity, Brilliant Blue G, P2X7 antagonists, norepinephrine, amygdala, striatum, ACTH, corticosterone, hematopoietic cells, gene expression, synaptic function, neuroplasticity, mood disorders
- MeSH terms
- Affect, Amygdala, Animals, Depression, Gene Expression Regulation, Male, Mice, Inbred C57BL, Stress, Psychological, Swimming, Microglia, Mice, Knockout, Mice, Receptors, Purinergic P2X7
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