{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:37:49Z","timestamp":1789659469022,"version":"4.0.1"},"reference-count":109,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research (MUR)","award":["2017NSXP8J"],"award-info":[{"award-number":["2017NSXP8J"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["GPR17ALS-1"],"award-info":[{"award-number":["GPR17ALS-1"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["MAANTID"],"award-info":[{"award-number":["MAANTID"]}]},{"name":"PRIN\u2014Progetti di Ricerca di Interesse Nazionale","award":["2017NSXP8J"],"award-info":[{"award-number":["2017NSXP8J"]}]},{"name":"PRIN\u2014Progetti di Ricerca di Interesse Nazionale","award":["GPR17ALS-1"],"award-info":[{"award-number":["GPR17ALS-1"]}]},{"name":"PRIN\u2014Progetti di Ricerca di Interesse Nazionale","award":["MAANTID"],"award-info":[{"award-number":["MAANTID"]}]},{"DOI":"10.13039\/501100007802","name":"Fondazione AriSLA, Italy","doi-asserted-by":"publisher","award":["2017NSXP8J"],"award-info":[{"award-number":["2017NSXP8J"]}],"id":[{"id":"10.13039\/501100007802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007802","name":"Fondazione AriSLA, Italy","doi-asserted-by":"publisher","award":["GPR17ALS-1"],"award-info":[{"award-number":["GPR17ALS-1"]}],"id":[{"id":"10.13039\/501100007802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007802","name":"Fondazione AriSLA, Italy","doi-asserted-by":"publisher","award":["MAANTID"],"award-info":[{"award-number":["MAANTID"]}],"id":[{"id":"10.13039\/501100007802","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e0 degli Studi di Milano","award":["2017NSXP8J"],"award-info":[{"award-number":["2017NSXP8J"]}]},{"name":"Universit\u00e0 degli Studi di Milano","award":["GPR17ALS-1"],"award-info":[{"award-number":["GPR17ALS-1"]}]},{"name":"Universit\u00e0 degli Studi di Milano","award":["MAANTID"],"award-info":[{"award-number":["MAANTID"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>With the umbrella term \u2018neurodevelopmental disorders\u2019 (NDDs) we refer to a plethora of congenital pathological conditions generally connected with cognitive, social behavior, and sensory\/motor alterations. Among the possible causes, gestational and perinatal insults have been demonstrated to interfere with the physiological processes necessary for the proper development of fetal brain cytoarchitecture and functionality. In recent years, several genetic disorders caused by mutations in key enzymes involved in purine metabolism have been associated with autism-like behavioral outcomes. Further analysis revealed dysregulated purine and pyrimidine levels in the biofluids of subjects with other NDDs. Moreover, the pharmacological blockade of specific purinergic pathways reversed the cognitive and behavioral defects caused by maternal immune activation, a validated and now extensively used rodent model for NDDs. Furthermore, Fragile X and Rett syndrome transgenic animal models as well as models of premature birth, have been successfully utilized to investigate purinergic signaling as a potential pharmacological target for these diseases. In this review, we examine results on the role of the P2 receptor signaling in the etiopathogenesis of NDDs. On this basis, we discuss how this evidence could be exploited to develop more receptor-specific ligands for future therapeutic interventions and novel prognostic markers for the early detection of these conditions.<\/jats:p>","DOI":"10.3390\/biom13050856","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T08:09:44Z","timestamp":1684397384000},"page":"856","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Altered Purinergic Signaling in Neurodevelopmental Disorders: Focus on P2 Receptors"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0844-1030","authenticated-orcid":false,"given":"Marta","family":"Boccazzi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmaceutical Sciences, Universit\u00e0 Degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-5418","authenticated-orcid":false,"given":"Stefano","family":"Raffaele","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 Degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7026-0384","authenticated-orcid":false,"given":"Thomas","family":"Zanettin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 Degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-3388","authenticated-orcid":false,"given":"Maria P.","family":"Abbracchio","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmaceutical Sciences, Universit\u00e0 Degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-842X","authenticated-orcid":false,"given":"Marta","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 Degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S2215-0366(16)30376-5","article-title":"Neurodevelopmental Disorders","volume":"4","author":"Thapar","year":"2017","journal-title":"Lancet Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.tins.2020.05.004","article-title":"Neurodevelopmental Disorders: From Genetics to Functional Pathways","volume":"43","author":"Parenti","year":"2020","journal-title":"Trends. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.molmed.2022.02.004","article-title":"COVID-19 in Pregnancy: Implications for Fetal Brain Development","volume":"28","author":"Shook","year":"2022","journal-title":"Trends. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nbd.2015.07.007","article-title":"Cellular and Molecular Introduction to Brain Development","volume":"92","author":"Jiang","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.neuron.2015.12.008","article-title":"The Cellular and Molecular Landscapes of the Developing Human Central Nervous System","volume":"89","author":"Silbereis","year":"2016","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0197-0186(00)00034-6","article-title":"Adenosine as a Neuromodulator and as a Homeostatic Regulator in the Nervous System: Different Roles, Different Sources and Different Receptors","volume":"38","author":"Cunha","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s11302-006-9016-0","article-title":"Roles of P2 Receptors in Glial Cells: Focus on Astrocytes","volume":"2","author":"Abbracchio","year":"2006","journal-title":"Purinergic. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3389\/fphar.2017.00941","article-title":"Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling New Pharmacological Approaches to Congenital Brain Diseases","volume":"8","author":"Fumagalli","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.neuropharm.2011.01.048","article-title":"Adenosine Hypothesis of Schizophrenia\u2014Opportunities for Pharmacotherapy","volume":"62","author":"Boison","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.neuropharm.2015.10.022","article-title":"Purines in Neurite Growth and Astroglia Activation","volume":"104","author":"Heine","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.1093\/cercor\/bhab188","article-title":"Adenosine A2A Receptors Contribute to the Radial Migration of Cortical Projection Neurons through the Regulation of Neuronal Polarization and Axon Formation","volume":"31","author":"Andres","year":"2021","journal-title":"Cereb. Cortex."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197ra104","DOI":"10.1126\/scitranslmed.3006258","article-title":"Adenosine Receptor Antagonists Including Caffeine Alter Fetal Brain Development in Mice","volume":"5","author":"Silva","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eabk2055","DOI":"10.1126\/science.abk2055","article-title":"Convergence of Adenosine and GABA Signaling for Synapse Stabilization during Development","volume":"374","author":"Zappettini","year":"2021","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14690","DOI":"10.1038\/s41598-022-18884-4","article-title":"Adenosine A2A Receptors Control Synaptic Remodeling in the Adult Brain","volume":"12","author":"Xu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.3389\/fphar.2020.625662","article-title":"New Insight into the Role of Adenosine in Demyelination, Stroke and Neuropathic Pain","volume":"11","author":"Coppi","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.neuropharm.2015.10.008","article-title":"Purinergic Receptors in Embryonic and Adult Neurogenesis","volume":"104","author":"Oliveira","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s12015-012-9372-9","article-title":"Extrinsic Purinergic Regulation of Neural Stem\/Progenitor Cells: Implications for CNS Development and Repair","volume":"8","author":"Ulrich","year":"2012","journal-title":"Stem. Cell. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111369","DOI":"10.1016\/j.celrep.2022.111369","article-title":"Microglial Control of Neuronal Development via Somatic Purinergic Junctions","volume":"40","author":"Schwarcz","year":"2022","journal-title":"Cell. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bcp.2009.09.014","article-title":"Astrocytes in the Damaged Brain: Molecular and Cellular Insights into Their Reactive Response and Healing Potential","volume":"79","author":"Buffo","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.neuropharm.2015.10.005","article-title":"CNS Remyelination as a Novel Reparative Approach to Neurodegenerative Diseases: The Roles of Purinergic Signaling and the P2Y-like Receptor GPR17","volume":"104","author":"Fumagalli","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0166-2236(00)01674-X","article-title":"ATP: An Extracellular Signaling Molecule between Neurons and Glia","volume":"23","author":"Fields","year":"2000","journal-title":"Trends. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9238","DOI":"10.1523\/JNEUROSCI.4001-11.2012","article-title":"Purinergic Signaling Promotes Proliferation of Adult Mouse Subventricular Zone Cells","volume":"32","author":"Suyama","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/glia.22614","article-title":"Purines Regulate Adult Brain Subventricular Zone Cell Functions: Contribution of Reactive Astrocytes","volume":"62","author":"Boccazzi","year":"2014","journal-title":"Glia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.bcp.2017.06.129","article-title":"Emerging Pharmacological Approaches to Promote Neurogenesis from Endogenous Glial Cells","volume":"141","author":"Boda","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1242\/jcs.091736","article-title":"Adenylate Cyclase 5 Coordinates the Action of ADP, P2Y1, P2Y13 and ATP-Gated P2X7 Receptors on Axonal Elongation","volume":"125","author":"Tapia","year":"2012","journal-title":"J. Cell. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1093\/hmg\/ddw248","article-title":"Neurodevelopmental Alterations and Seizures Developed by Mouse Model of Infantile Hypophosphatasia Are Associated with Purinergic Signalling Deregulation","volume":"25","author":"Engel","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.semcdb.2018.12.001","article-title":"Purinergic Signalling and Brain Development","volume":"95","author":"Rodrigues","year":"2019","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2174\/1570159X20666220706100136","article-title":"Epilepsy and Autism Spectrum Disorder (ASD): The Underlying Mechanisms and Therapy Targets Related to Adenosine","volume":"21","author":"Guo","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fncel.2023.1120532","article-title":"The Adenosine Hypothesis of Schizophrenia into Its Third Decade: From Neurochemical Imbalance to Early Life Etiological Risks","volume":"17","author":"Singer","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pasquini, S., Contri, C., Merighi, S., Gessi, S., Borea, P.A., Varani, K., and Vincenzi, F. (2022). Adenosine Receptors in Neuropsychiatric Disorders: Fine Regulators of Neurotransmission and Potential Therapeutic Targets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031219"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10409238.2020.1832438","article-title":"Human de Novo Purine Biosynthesis","volume":"56","author":"Pareek","year":"2021","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/0002-9343(64)90104-4","article-title":"A Familial Disorder of Uric Acid Metabolism and Central Nervous System Function","volume":"36","author":"Lesch","year":"1964","journal-title":"Am. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/YCO.0000000000000388","article-title":"Lesch\u2013Nyhan Syndrome and Its Variants","volume":"31","author":"Harris","year":"2018","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0022-3476(69)80004-1","article-title":"A New Disorder of Purine Metabolism with Behavioral Manifestations","volume":"74","author":"Nyhan","year":"1969","journal-title":"J. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13229-016-0109-5","article-title":"Urinary Metabolomics of Young Italian Autistic Children Supports Abnormal Tryptophan and Purine Metabolism","volume":"7","author":"Gevi","year":"2016","journal-title":"Mol. Autism."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jpba.2018.01.007","article-title":"Identification of Metabolic Pathway Disturbances Using Multimodal Metabolomics in Autistic Disorders in a Middle Eastern Population","volume":"152","author":"Bitar","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s42003-019-0485-4","article-title":"Metabolome Signature of Autism in the Human Prefrontal Cortex","volume":"2","author":"Kurochkin","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6105608","DOI":"10.1155\/2020\/6105608","article-title":"Untargeted Metabolomic Profiling Using UHPLC-QTOF\/MS Reveals Metabolic Alterations Associated with Autism","volume":"2020","author":"Liang","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mussap, M., Siracusano, M., Noto, A., Fattuoni, C., Riccioni, A., Rajula, H.S.R., Fanos, V., Curatolo, P., Barberini, L., and Mazzone, L. (2020). The Urine Metabolome of Young Autistic Children Correlates with Their Clinical Profile Severity. Metabolites, 10.","DOI":"10.3390\/metabo10110476"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1089871","DOI":"10.3389\/fnmol.2023.1089871","article-title":"Purine Signaling Pathway Dysfunction in Autism Spectrum Disorders: Evidence from Multiple Omics Data","volume":"16","author":"Dai","year":"2023","journal-title":"Front. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/15257770.2016.1147579","article-title":"A Review of the Implication of Hypoxanthine Excess in the Physiopathology of Lesch\u2013Nyhan Disease","volume":"35","author":"Torres","year":"2016","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/ijnp\/pyac026","article-title":"Elevated Serum Purine Levels in Schizophrenia: A Reverse Translational Study to Identify Novel Inflammatory Biomarkers","volume":"25","author":"Baranyi","year":"2022","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41537-022-00312-1","article-title":"Altered Purinergic Receptor Expression in the Frontal Cortex in Schizophrenia","volume":"8","author":"Alnafisah","year":"2022","journal-title":"Schizophrenia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.tins.2008.11.003","article-title":"Purinergic Signalling in Inflammation of the Central Nervous System","volume":"32","author":"Ceruti","year":"2009","journal-title":"Trends. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fnins.2015.00148","article-title":"ATP as a Multi-Target Danger Signal in the Brain","volume":"9","author":"Rodrigues","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e400","DOI":"10.1038\/tp.2014.33","article-title":"Reversal of Autism-like Behaviors and Metabolism in Adult Mice with Single-Dose Antipurinergic Therapy","volume":"4","author":"Naviaux","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/bdr2.1416","article-title":"Maternal Immune Activation, Central Nervous System Development and Behavioral Phenotypes","volume":"110","author":"Minakova","year":"2018","journal-title":"Birth. Defects. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1399-5618.2010.00849.x","article-title":"Prenatal Exposure to Influenza and Major Affective Disorder","volume":"12","author":"Selten","year":"2010","journal-title":"Bipolar. Disord."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.schres.2016.11.006","article-title":"The Serological Evidence for Maternal Influenza as Risk Factor for Psychosis in Offspring Is Insufficient: Critical Review and Meta-Analysis","volume":"183","author":"Selten","year":"2017","journal-title":"Schizophr. Res."},{"key":"ref_50","first-page":"643","article-title":"Maternal Immune Activation and Abnormal Brain Development across CNS Disorders","volume":"10","author":"Knuesel","year":"2014","journal-title":"Nat. Publ. Group"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.biopsych.2013.07.011","article-title":"Prenatal Poly(I:C) Exposure and Other Developmental Immune Activation Models in Rodent Systems","volume":"75","author":"Meyer","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1126\/science.1228261","article-title":"Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice","volume":"339","author":"Giovanoli","year":"2013","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1071976","DOI":"10.3389\/fnins.2022.1071976","article-title":"A Comprehensive Approach to Modeling Maternal Immune Activation in Rodents","volume":"16","author":"Bucknor","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.neubiorev.2021.07.015","article-title":"Maternal Immune Activation in Rodent Models: A Systematic Review of Neurodevelopmental Changes in Gene Expression and Epigenetic Modulation in the Offspring Brain","volume":"129","author":"Woods","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbi.2012.07.008","article-title":"Maternal Immune Activation Causes Age- and Region-Specific Changes in Brain Cytokines in Offspring throughout Development","volume":"31","author":"Garay","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.placenta.2011.05.001","article-title":"How Does Variability of Immune System Genes Affect Placentation?","volume":"32","author":"Colucci","year":"2011","journal-title":"Placenta"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2018.12.002","article-title":"Brain Changes in a Maternal Immune Activation Model of Neurodevelopmental Brain Disorders","volume":"175","author":"Bergdolt","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/dvdy.24612","article-title":"Maternal Immune Activation in Neurodevelopmental Disorders","volume":"247","author":"Solek","year":"2018","journal-title":"Dev. Dyn."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.neubiorev.2020.04.012","article-title":"Maternal Immune Activation by Poly I:C as a Preclinical Model for Neurodevelopmental Disorders: A Focus on Autism and Schizophrenia","volume":"113","author":"Haddad","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.pharmthera.2015.01.001","article-title":"The Poly(I:C)-Induced Maternal Immune Activation Model in Preclinical Neuropsychiatric Drug Discovery","volume":"149","author":"Reisinger","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Naviaux, R.K., Zolkipli, Z., Wang, L., Nakayama, T., Naviaux, J.C., Le, T.P., Schuchbauer, M.A., Rogac, M., Tang, Q., and Dugan, L.L. (2013). Antipurinergic Therapy Corrects the Autism-like Features in the Poly(IC) Mouse Model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057380"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.psyneuen.2018.08.015","article-title":"Emerging Role of the P2X7-NLRP3-IL1\u03b2 Pathway in Mood Disorders","volume":"98","author":"Bhattacharya","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.pneurobio.2006.03.007","article-title":"P2X7 Receptors in the Nervous System","volume":"78","author":"Vizi","year":"2006","journal-title":"Prog. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"C832","DOI":"10.1152\/ajpcell.00053.2020","article-title":"Purinergic Signaling, DAMPs, and Inflammation","volume":"318","author":"Sarti","year":"2020","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"662935","DOI":"10.3389\/fncel.2021.662935","article-title":"Role of P2X7 Receptors in Immune Responses during Neurodegeneration","volume":"15","author":"Petiz","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_66","first-page":"2542","article-title":"P2X7 Receptors Drive Poly(I:C) Induced Autism-like Behavior in Mice","volume":"39","author":"Otrokocsi","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bbi.2022.01.015","article-title":"Maternal P2X7 Receptor Inhibition Prevents Autism-like Phenotype in Male Mouse Offspring through the NLRP3-IL-1\u03b2 Pathway","volume":"101","author":"Tod","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1523\/JNEUROSCI.0805-22.2022","article-title":"Dual Role of the P2X7 Receptor in Dendritic Outgrowth during Physiological and Pathological Brain Development","volume":"43","author":"Huang","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/acn3.424","article-title":"Low-Dose Suramin in Autism Spectrum Disorder: A Small, Phase I\/II, Randomized Clinical Trial","volume":"4","author":"Naviaux","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"114461","DOI":"10.1016\/j.bcp.2021.114461","article-title":"Therapeutic Potential of Stem Cells for Preterm Infant Brain Damage: Can We Move from the Heterogeneity of Preclinical and Clinical Studies to Established Therapeutics?","volume":"186","author":"Passera","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1016\/S2214-109X(18)30451-0","article-title":"Global, Regional, and National Estimates of Levels of Preterm Birth in 2014: A Systematic Review and Modelling Analysis","volume":"7","author":"Chawanpaiboon","year":"2019","journal-title":"Lancet Glob. Health"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.schres.2021.04.007","article-title":"Adult Outcome of Preterm Birth: Implications for Neurodevelopmental Theories of Psychosis","volume":"247","author":"Vanes","year":"2022","journal-title":"Schizophr. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"881674","DOI":"10.3389\/fphys.2022.881674","article-title":"Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity","volume":"13","author":"Favrais","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1038\/sj.emboj.7601341","article-title":"The Orphan Receptor GPR17 Identified as a New Dual Uracil Nucleotides\/Cysteinyl-Leukotrienes Receptor","volume":"25","author":"Ciana","year":"2006","journal-title":"EMBO J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.brainres.2012.09.033","article-title":"Periventricular Leukomalacia Long-Term Prognosis May Be Improved by Treatment with UDP-Glucose, GDNF, and Memantine in Neonatal Rats","volume":"1486","author":"Mao","year":"2012","journal-title":"Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.neuroscience.2014.10.012","article-title":"Treatment with UDP-Glucose, GDNF, and Memantine Promotes SVZ and White Matter Self-Repair by Endogenous Glial Progenitor Cells in Neonatal Rats with Ischemic PVL","volume":"284","author":"Li","year":"2015","journal-title":"Neuroscience"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7314","DOI":"10.1080\/21655979.2021.1979352","article-title":"Knockdown of G Protein-Coupled Receptor-17 (GPR17) Facilitates the Regeneration and Repair of Myelin Sheath Post-Periventricular Leukomalacia (PVL)","volume":"12","author":"He","year":"2021","journal-title":"Bioengineered"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/ana.22489","article-title":"Systemic Inflammation Disrupts the Developmental Program of White Matter","volume":"70","author":"Favrais","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41419-021-03446-9","article-title":"The Immune-Inflammatory Response of Oligodendrocytes in a Murine Model of Preterm White Matter Injury: The Role of TLR3 Activation","volume":"12","author":"Boccazzi","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10593","DOI":"10.1074\/jbc.M110.162867","article-title":"Phenotypic Changes, Signaling Pathway, and Functional Correlates of GPR17-Expressing Neural Precursor Cells during Oligodendrocyte Differentiation","volume":"286","author":"Fumagalli","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1074\/jbc.M112.404996","article-title":"The Regulated Expression, Intracellular Trafficking, and Membrane Recycling of the P2Y-like Receptor GPR17 in Oli-Neu Oligodendroglial Cells","volume":"288","author":"Fratangeli","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1021\/ml400399f","article-title":"Development of [3H]2-Carboxy-4,6-Dichloro-1 H-Indole-3-Propionic Acid ([3H]PSB-12150): A Useful Tool for Studying GPR17","volume":"5","author":"Ritter","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.phrs.2019.02.025","article-title":"Improvement of Fiber Connectivity and Functional Recovery after Stroke by Montelukast, an Available and Safe Anti-Asthmatic Drug","volume":"142","author":"Gelosa","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bonfanti, E., Bonifacino, T., Raffaele, S., Milanese, M., Morgante, E., Bonanno, G., Abbracchio, M.P., and Fumagalli, M. (2020). Abnormal Upregulation of GPR17 Receptor Contributes to Oligodendrocyte Dysfunction in SOD1 G93A Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072395"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1038\/ncomms9466","article-title":"Structural and Functional Rejuvenation of the Aged Brain by an Approved Anti-Asthmatic Drug","volume":"6","author":"Marschallinger","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e13335","DOI":"10.1111\/acel.13335","article-title":"Functional Genomic Analyses Highlight a Shift in Gpr17-Regulated Cellular Processes in Oligodendrocyte Progenitor Cells and Underlying Myelin Dysregulation in the Aged Mouse Cerebrum","volume":"20","author":"Rivera","year":"2021","journal-title":"Aging Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1080\/15476286.2020.1809186","article-title":"RNA-Binding Proteins in Neurological Development and Disease","volume":"18","author":"Prashad","year":"2021","journal-title":"RNA Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/0092-8674(91)90125-I","article-title":"Absence of Expression of the FMR-1 Gene in Fragile X Syndrome","volume":"66","author":"Pieretti","year":"1991","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"118","DOI":"10.5582\/irdr.2014.01024","article-title":"Modeling Fragile X Syndrome in the Fmr1 Knockout Mouse","volume":"3","author":"Kazdoba","year":"2014","journal-title":"Intractable Rare. Dis. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2040-2392-6-1","article-title":"Antipurinergic Therapy Corrects the Autism-like Features in the Fragile X (Fmr1 Knockout) Mouse Model","volume":"6","author":"Naviaux","year":"2015","journal-title":"Mol. Autism."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.biopsych.2016.08.036","article-title":"Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model of Fragile X Syndrome","volume":"82","author":"Hodges","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1523\/JNEUROSCI.5027-09.2010","article-title":"Astrocytes Prevent Abnormal Neuronal Development in the Fragile X Mouse","volume":"30","author":"Jacobs","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1002\/glia.23997","article-title":"Astrocyte-Mediated Purinergic Signaling Is Upregulated in a Mouse Model of Fragile X Syndrome","volume":"69","author":"Reynolds","year":"2021","journal-title":"Glia"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3389\/fnmol.2018.00272","article-title":"Regulation of IL-6 Secretion by Astrocytes via TLR4 in the Fragile X Mouse Model","volume":"11","author":"Krasovska","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3389\/fncel.2021.764761","article-title":"Rett Syndrome and Fragile X Syndrome: Different Etiology with Common Molecular Dysfunctions","volume":"15","author":"Bach","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/s41467-020-15590-5","article-title":"P2X7 Receptor Inhibition Ameliorates Dendritic Spine Pathology and Social Behavioral Deficits in Rett Syndrome Mice","volume":"11","author":"Silva","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/nn.2410","article-title":"The Oligodendrocyte-Specific G Protein-Coupled Receptor GPR17 Is a Cell-Intrinsic Timer of Myelination","volume":"12","author":"Chen","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Angelini, J., Marangon, D., Raffaele, S., Lecca, D., and Abbracchio, M.P. (2021). The Distribution of Gpr17-Expressing Cells Correlates with White Matter Inflammation Status in Brain Tissues of Multiple Sclerosis Patients. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094574"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s11302-013-9366-3","article-title":"Changes of the GPR17 Receptor, a New Target for Neurorepair, in Neurons and Glial Cells in Patients with Traumatic Brain Injury","volume":"9","author":"Franke","year":"2013","journal-title":"Purinergic. Signal."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"50","DOI":"10.5582\/irdr.2016.01097","article-title":"Expression of GPR17, a Regulator of Oligodendrocyte Differentiation and Maturation, in Nasu-Hakola Disease Brains","volume":"6","author":"Satoh","year":"2017","journal-title":"Intractable Rare. Dis. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1002\/glia.21237","article-title":"The GPR17 Receptor in NG2 Expressing Cells: Focus on in Vivo Cell Maturation and Participation in Acute Trauma and Chronic Damage","volume":"59","author":"Boda","year":"2011","journal-title":"Glia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.celrep.2014.09.037","article-title":"Sorting Nexin 27 Regulates A\u03b2 Production through Modulating \u03b3-Secretase Activity","volume":"9","author":"Wang","year":"2014","journal-title":"Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nm.3117","article-title":"Loss of Sorting Nexin 27 Contributes to Excitatory Synaptic Dysfunction by Modulating Glutamate Receptor Recycling in Down\u2019s Syndrome","volume":"19","author":"Wang","year":"2013","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"642378","DOI":"10.3389\/fcell.2021.642378","article-title":"Toward Understanding the Molecular Role of SNX27\/Retromer in Human Health and Disease","volume":"9","author":"Chandra","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/glia.23015","article-title":"SNX27, a Protein Involved in down Syndrome, Regulates GPR17 Trafficking and Oligodendrocyte Differentiation","volume":"64","author":"Meraviglia","year":"2016","journal-title":"Glia"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/glia.23868","article-title":"White Matter Alterations in Williams Syndrome Related to Behavioral and Motor Impairments","volume":"69","author":"Nir","year":"2021","journal-title":"Glia"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/s41593-019-0380-9","article-title":"Neuronal Deletion of Gtf2i, Associated with Williams Syndrome, Causes Behavioral and Myelin Alterations Rescuable by a Remyelinating Drug","volume":"22","author":"Barak","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s41380-022-01921-z","article-title":"In Individuals with Williams Syndrome, Dysregulation of Methylation in Non-Coding Regions of Neuronal and Oligodendrocyte DNA Is Associated with Pathology and Cortical Development","volume":"28","author":"Trangle","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1021\/jm901691y","article-title":"Frontal Affinity Chromatography-Mass Spectrometry Useful for Characterization of New Ligands for GPR17 Receptor","volume":"53","author":"Calleri","year":"2010","journal-title":"J. Med. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/5\/856\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:37:48Z","timestamp":1760125068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/5\/856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":109,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["biom13050856"],"URL":"https:\/\/doi.org\/10.3390\/biom13050856","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,18]]}}}