{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:07:52Z","timestamp":1788538072526,"version":"build-2803163510"},"reference-count":120,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["11230898"],"award-info":[{"award-number":["11230898"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["11240855"],"award-info":[{"award-number":["11240855"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["3200655"],"award-info":[{"award-number":["3200655"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ANID-MILENIO","award":["NCN2023_032"],"award-info":[{"award-number":["NCN2023_032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett syndrome (RTT) is a severe neurodevelopmental disorder caused primarily by mutations in the gene encoding the methyl-CpG-binding protein 2 (Mecp2). Mecp2 binds to methylated cytosines, playing a crucial role in chromatin organization and transcriptional regulation. At the neurobiological level, RTT is characterized by dendritic spine dysgenesis and altered excitation\u2013inhibition balance, drawing attention to the mechanisms that scale from mutations in a nuclear protein to altered neuronal connectivity. Although Mecp2 dysfunction disrupts multiple neuronal processes, emerging evidence highlights altered calcium (Ca2+) signaling as a central contributor to RTT pathophysiology. This review explores the link between Mecp2 and Ca2+ regulation by highlighting how Mecp2 affects Ca2+-dependent transcriptional pathways, while Ca2+ modulates Mecp2 function by inducing post-translational modifications. We discuss this crosstalk in light of evidence from RTT models, with a particular focus on the brain-derived neurotrophic factor BDNF-miR132-Mecp2 axis and the dysregulation of ryanodine receptors (RyRs). Additionally, we examine how these perturbations contribute to the reduced structural plasticity and the altered activity-driven gene expression that characterizes RTT. Understanding the intersection between Mecp2 function and Ca2+ homeostasis will provide critical insights into RTT pathogenesis and potential therapeutic targets aimed at restoring neuronal connectivity.<\/jats:p>","DOI":"10.3390\/ijms262110490","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:16:24Z","timestamp":1761729384000},"page":"10490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Ca2+ Bridge: From Neurons to Circuits in Rett Syndrome"],"prefix":"10.3390","volume":"26","author":[{"given":"Luis","family":"Molina Calistro","sequence":"first","affiliation":[{"name":"Facultad de Ciencias, Universidad San Sebasti\u00e1n, Lago Panguipulli 1390, Puerto Montt 5501842, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yennyfer","family":"Arancibia","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad San Sebasti\u00e1n, Lago Panguipulli 1390, Puerto Montt 5501842, Chile"},{"name":"Millennium Nucleus of Neuroepigenetics and Plasticity (EpiNeuro), Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad San Sebasti\u00e1n, Lago Panguipulli 1390, Puerto Montt 5501842, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-2920","authenticated-orcid":false,"given":"Rodrigo Flavio","family":"Torres","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad San Sebasti\u00e1n, Lago Panguipulli 1390, Puerto Montt 5501842, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/1073858403260995","article-title":"Rett Syndrome: A Prototypical Neurodevelopmental Disorder","volume":"10","author":"Neul","year":"2004","journal-title":"Neuroscientist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jpeds.2005.10.037","article-title":"Rett Syndrome in Australia: A Review of the Epidemiology","volume":"148","author":"Laurvick","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00431-007-0569-x","article-title":"The Diagnosis of Autism in a Female: Could It Be Rett Syndrome?","volume":"167","author":"Young","year":"2008","journal-title":"Eur. J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The Story of Rett Syndrome: From Clinic to Neurobiology","volume":"56","author":"Chahrour","year":"2007","journal-title":"Neuron"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pepe, G., Coco, R., Corica, D., Luppino, G., Morabito, L.A., Lugar\u00e0, C., Abbate, T., Zirilli, G., Aversa, T., and Stagi, S. (2024). Endocrine Disorders in Rett Syndrome: A Systematic Review of the Literature. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1477227"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ziemka-Nalecz, M., Pawelec, P., Ziabska, K., and Zalewska, T. (2023). Sex Differences in Brain Disorders. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914571"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA Methylation Patterns and Epigenetic Memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/nn.2900","article-title":"Neuronal Activity Modifies the DNA Methylation Landscape in the Adult Brain","volume":"14","author":"Guo","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1074\/jbc.M007224200","article-title":"DNA Recognition by the Methyl-CpG Binding Domain of MeCP2","volume":"276","author":"Free","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett Syndrome Is Caused by Mutations in X-Linked MECP2, Encoding Methyl-CpG-Binding Protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.jmb.2019.10.004","article-title":"The Molecular Basis of MeCP2 Function in the Brain","volume":"432","author":"Tillotson","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/cne.21264","article-title":"Differential Distribution of the MeCP2 Splice Variants in the Postnatal Mouse Brain","volume":"501","author":"Dragich","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/ejhg.2011.145","article-title":"Transgenic Complementation of MeCP2 Deficiency: Phenotypic Rescue of Mecp2-Null Mice by Isoform-Specific Transgenes","volume":"20","author":"Kerr","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddaa154","article-title":"Regulation, Diversity and Function of MECP2 Exon and 3\u2032UTR Isoforms","volume":"29","author":"Rodrigues","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41583-025-00926-1","article-title":"Exploring the Complexity of MECP2 Function in Rett Syndrome","volume":"26","author":"Liu","year":"2025","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7008","DOI":"10.1021\/bi990224y","article-title":"The Methyl-CpG Binding Transcriptional Repressor MeCP2 Stably Associates with Nucleosomal DNA","volume":"38","author":"Chandler","year":"1999","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/30764","article-title":"Transcriptional Repression by the Methyl-CpG-Binding Protein MeCP2 Involves a Histone Deacetylase Complex","volume":"393","author":"Nan","year":"1998","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","article-title":"MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription","volume":"320","author":"Chahrour","year":"2008","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.cell.2012.11.022","article-title":"MeCP2 Binds to 5hmC Enriched within Active Genes and Accessible Chromatin in the Nervous System","volume":"151","author":"Ayata","year":"2012","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nature14319","article-title":"Disruption of DNA Methylation-Dependent Long Gene Repression in Rett Syndrome","volume":"522","author":"Gabel","year":"2015","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1093\/hmg\/ddp181","article-title":"Mouse Models of MeCP2 Disorders Share Gene Expression Changes in the Cerebellum and Hypothalamus","volume":"18","author":"Chahrour","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.nbd.2013.08.001","article-title":"Loss of MeCP2 Function Is Associated with Distinct Gene Expression Changes in the Striatum","volume":"59","author":"Zhao","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.1073\/pnas.1411269112","article-title":"Reading the Unique DNA Methylation Landscape of the Brain: Non-CpG Methylation, Hydroxymethylation, and MeCP2","volume":"112","author":"Kinde","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ajmg.a.20571","article-title":"Phenotypic Manifestations of MECP2 Mutations in Classical and Atypical Rett Syndrome","volume":"126A","author":"Schanen","year":"2004","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/brain\/awy323","article-title":"Towards a Better Diagnosis and Treatment of Rett Syndrome: A Model Synaptic Disorder","volume":"142","author":"Banerjee","year":"2019","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/85899","article-title":"A Mouse Mecp2-Null Mutation Causes Neurological Symptoms That Mimic Rett Syndrome","volume":"27","author":"Guy","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_27","first-page":"5","article-title":"Beyond Widespread Mecp2 Deletions to Model Rett Syndrome: Conditional Spatio-Temporal Knockout, Single-Point Mutations and Transgenic Rescue Mice","volume":"2012","author":"Li","year":"2012","journal-title":"Autism Open Access"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.nbd.2005.07.005","article-title":"Hippocampal Synaptic Plasticity Is Impaired in the Mecp2-Null Mouse Model of Rett Syndrome","volume":"21","author":"Asaka","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kerr, B., Silva, P.A., Walz, K., and Young, J.I. (2010). Unconventional Transcriptional Response to Environmental Enrichment in a Mouse Model of Rett Syndrome. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011534"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bach, S., Shovlin, S., Moriarty, M., Bardoni, B., and Tropea, D. (2021). Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions. Front. Cell Neurosci., 15.","DOI":"10.3389\/fncel.2021.764761"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1097\/00001756-199407000-00025","article-title":"Rett Syndrome: 3-D Confocal Microscopy of Cortical Pyramidal Dendrites and Afferents","volume":"5","author":"Belichenko","year":"1994","journal-title":"Neuroreport"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10021","DOI":"10.1523\/JNEUROSCI.1316-12.2012","article-title":"MeCP2 Is Critical for Maintaining Mature Neuronal Networks and Global Brain Anatomy during Late Stages of Postnatal Brain Development and in the Mature Adult Brain","volume":"32","author":"Nguyen","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Torres, R.F., Hidalgo, C., and Kerr, B. (2017). Mecp2 Mediates Experience-Dependent Transcriptional Upregulation of Ryanodine Receptor Type-3. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00188"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Landi, S., Putignano, E., Boggio, E.M., Giustetto, M., Pizzorusso, T., and Ratto, G.M. (2011). The Short-Time Structural Plasticity of Dendritic Spines Is Altered in a Model of Rett Syndrome. Sci. Rep., 1.","DOI":"10.1038\/srep00045"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1126\/science.1089071","article-title":"Postnatal Neurodevelopmental Disorders: Meeting at the Synapse?","volume":"302","author":"Zoghbi","year":"2003","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xu, X., Miller, E.C., and Pozzo-Miller, L. (2014). Dendritic Spine Dysgenesis in Rett Syndrome. Front. Neuroanat., 8.","DOI":"10.3389\/fnana.2014.00097"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6033","DOI":"10.1073\/pnas.0401626101","article-title":"Expression of MeCP2 in Postmitotic Neurons Rescues Rett Syndrome in Mice","volume":"101","author":"Luikenhuis","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1016\/j.ymthe.2023.07.013","article-title":"Novel MECP2 Gene Therapy Is Effective in a Multicenter Study Using Two Mouse Models of Rett Syndrome and Is Safe in Non-Human Primates","volume":"31","author":"Powers","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5982625","DOI":"10.1155\/2019\/5982625","article-title":"Writers and Readers of DNA Methylation\/Hydroxymethylation in Physiological Aging and Its Impact on Cognitive Function","volume":"2019","author":"Torres","year":"2019","journal-title":"Neural Plast."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuron.2024.11.006","article-title":"Acute MeCP2 Loss in Adult Mice Reveals Transcriptional and Chromatin Changes That Precede Neurological Dysfunction and Inform Pathogenesis","volume":"113","author":"Bajikar","year":"2024","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1093\/hmg\/dds208","article-title":"Postnatal Inactivation Reveals Enhanced Requirement for MeCP2 at Distinct Age Windows","volume":"21","author":"Cheval","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13529","DOI":"10.1523\/JNEUROSCI.3077-12.2012","article-title":"A Critical and Cell-Autonomous Role for MeCP2 in Synaptic Scaling Up","volume":"32","author":"Blackman","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7436","DOI":"10.1093\/cercor\/bhad050","article-title":"Mecp2 Deletion Results in Profound Alterations of Developmental and Adult Functional Connectivity","volume":"33","author":"Rahn","year":"2023","journal-title":"Cereb. Cortex"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12560","DOI":"10.1073\/pnas.0506071102","article-title":"Reduced Cortical Activity Due to a Shift in the Balance between Excitation and Inhibition in a Mouse Model of Rett Syndrome","volume":"102","author":"Dani","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.neuron.2020.02.015","article-title":"Whole-Neuron Synaptic Mapping Reveals Spatially Precise Excitatory\/Inhibitory Balance Limiting Dendritic and Somatic Spiking","volume":"106","author":"Iascone","year":"2020","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nn1206","article-title":"Local Structural Balance and Functional Interaction of Excitatory and Inhibitory Synapses in Hippocampal Dendrites","volume":"7","author":"Liu","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neuron.2007.08.018","article-title":"MeCP2 Controls Excitatory Synaptic Strength by Regulating Glutamatergic Synapse Number","volume":"56","author":"Chao","year":"2007","journal-title":"Neuron"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1093\/cercor\/bhv002","article-title":"Mechanisms of Functional Hypoconnectivity in the Medial Prefrontal Cortex of Mecp2 Null Mice","volume":"26","author":"Sceniak","year":"2016","journal-title":"Cereb. Cortex"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11263","DOI":"10.1523\/JNEUROSCI.1019-09.2009","article-title":"Intact Long-Term Potentiation but Reduced Connectivity between Neocortical Layer 5 Pyramidal Neurons in a Mouse Model of Rett Syndrome","volume":"29","author":"Dani","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.cub.2006.02.062","article-title":"MeCP2-Dependent Transcriptional Repression Regulates Excitatory Neurotransmission","volume":"16","author":"Nelson","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuron.2011.03.001","article-title":"Experience-Dependent Retinogeniculate Synapse Remodeling Is Abnormal in MeCP2-Deficient Mice","volume":"70","author":"Noutel","year":"2011","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1523\/JNEUROSCI.0175-11.2012","article-title":"The Rett Syndrome Protein MeCP2 Regulates Synaptic Scaling","volume":"32","author":"Qiu","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nrn3531","article-title":"Nuclear Calcium Signalling in the Regulation of Brain Function","volume":"14","author":"Bading","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hagenston, A.M., and Bading, H. (2011). Calcium Signaling in Synapse-to-Nucleus Communication. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a004564"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2102265118","DOI":"10.1073\/pnas.2102265118","article-title":"RyR-Mediated Ca2+ Release Elicited by Neuronal Activity Induces Nuclear Ca2+ Signals, CREB Phosphorylation, and Npas4\/RyR2 Expression","volume":"118","author":"Lobos","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"30967","DOI":"10.1074\/jbc.M112.382507","article-title":"Nuclear Calcium Signaling Controls Methyl-CpG-Binding Protein 2 (MeCP2) Phosphorylation on Serine 421 Following Synaptic Activity","volume":"287","author":"Buchthal","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/85109","article-title":"Nuclear Calcium Signaling Controls CREB-Mediated Gene Expression Triggered by Synaptic Activity","volume":"4","author":"Hardingham","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9093","DOI":"10.1073\/pnas.0803072105","article-title":"An Activity-Regulated microRNA Controls Dendritic Plasticity by down-Regulating p250GAP","volume":"105","author":"Wayman","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111386","DOI":"10.1016\/j.brainresbull.2025.111386","article-title":"Interpreting the Rich Dialogue between Astrocytes and Neurons: An Overview in Rett Syndrome","volume":"227","author":"Postogna","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/ddad150","article-title":"MeCP2 Ubiquitination and Sumoylation, in Search of a Function","volume":"33","author":"Kalani","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bellini, E., Pavesi, G., Barbiero, I., Bergo, A., Chandola, C., Nawaz, M.S., Rusconi, L., Stefanelli, G., Strollo, M., and Valente, M.M. (2014). MeCP2 Post-Translational Modifications: A Mechanism to Control Its Involvement in Synaptic Plasticity and Homeostasis?. Front. Cell Neurosci., 8.","DOI":"10.3389\/fncel.2014.00236"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1073\/pnas.0811648106","article-title":"Phosphorylation of MeCP2 at Serine 80 Regulates Its Chromatin Association and Neurological Function","volume":"106","author":"Tao","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1126\/science.1086446","article-title":"Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2","volume":"302","author":"Chen","year":"2003","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e2310344120","DOI":"10.1073\/pnas.2310344120","article-title":"Activity-Induced MeCP2 Phosphorylation Regulates Retinogeniculate Synapse Refinement","volume":"120","author":"Tzeng","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1073\/pnas.0901518106","article-title":"The Yin and Yang of MeCP2 Phosphorylation","volume":"106","author":"Chao","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neuron.2011.09.017","article-title":"MeCP2: Phosphorylated Locally, Acting Globally","volume":"72","author":"Rutlin","year":"2011","journal-title":"Neuron"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00441-020-03226-5","article-title":"BDNF Signaling during the Lifetime of Dendritic Spines","volume":"382","author":"Zagrebelsky","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.neuron.2006.09.037","article-title":"Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation","volume":"52","author":"Zhou","year":"2006","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neuron.2011.08.022","article-title":"Genome-Wide Activity-Dependent MeCP2 Phosphorylation Regulates Nervous System Development and Function","volume":"72","author":"Cohen","year":"2011","journal-title":"Neuron"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.molcel.2010.01.030","article-title":"Neuronal MeCP2 Is Expressed at near Histone-Octamer Levels and Globally Alters the Chromatin State","volume":"37","author":"Skene","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1093\/hmg\/ddh282","article-title":"Mild Overexpression of MeCP2 Causes a Progressive Neurological Disorder in Mice","volume":"13","author":"Collins","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.mcn.2009.10.005","article-title":"An Activity-Induced microRNA Controls Dendritic Spine Formation by Regulating Rac1-PAK Signaling","volume":"43","author":"Impey","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4742","DOI":"10.1093\/nar\/gks151","article-title":"miR-212\/132 Expression and Functions: Within and beyond the Neuronal Compartment","volume":"40","author":"Wanet","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"16426","DOI":"10.1073\/pnas.0508448102","article-title":"A cAMP-Response Element Binding Protein-Induced microRNA Regulates Neuronal Morphogenesis","volume":"102","author":"Vo","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hansen, K.F., Sakamoto, K., Wayman, G.A., Impey, S., and Obrietan, K. (2010). Transgenic miR132 Alters Neuronal Spine Density and Impairs Novel Object Recognition Memory. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015497"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.biocel.2011.10.015","article-title":"MicroRNA212\/132 Family: Molecular Transducer of Neuronal Function and Plasticity","volume":"44","author":"Tognini","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1523\/JNEUROSCI.2884-13.2014","article-title":"The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation","volume":"34","author":"Lesiak","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/hipo.22123","article-title":"In Vivo Knockdown of Hippocampal miR-132 Expression Impairs Memory Acquisition of Trace Fear Conditioning","volume":"23","author":"Wang","year":"2013","journal-title":"Hippocampus"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/nn2010","article-title":"Homeostatic Regulation of MeCP2 Expression by a CREB-Induced microRNA","volume":"10","author":"Klein","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.3892\/mmr.2015.4104","article-title":"MeCP2 Controls Hippocampal Brain-Derived Neurotrophic Factor Expression via Homeostatic Interactions with microRNA-132 in Rats with Depression","volume":"12","author":"Su","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2174\/1567202614666171101115308","article-title":"miR-132 Down-Regulates Methyl CpG Binding Protein 2 (MeCP2) During Cognitive Dysfunction Following Chronic Cerebral Hypoperfusion","volume":"14","author":"Yao","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Tong, L., Li, M.-D., Nie, P.-Y., Chen, Y., Chen, Y.-L., and Ji, L.-L. (2021). miR-132 Downregulation Alleviates Behavioral Impairment of Rats Exposed to Single Prolonged Stress, Reduces the Level of Apoptosis in PFC, and Upregulates the Expression of MeCP2 and BDNF. Neurobiol. Stress., 14.","DOI":"10.1016\/j.ynstr.2021.100311"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.celrep.2017.03.057","article-title":"miR-132\/212 Modulates Seasonal Adaptation and Dendritic Morphology of the Central Circadian Clock","volume":"19","author":"Chiang","year":"2017","journal-title":"Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"F1129","DOI":"10.1152\/ajprenal.00087.2018","article-title":"MicroRNA-132 Controls Water Homeostasis through Regulating MECP2-Mediated Vasopressin Synthesis","volume":"315","author":"Bijkerk","year":"2018","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Pejhan, S., Del Bigio, M.R., and Rastegar, M. (2020). The MeCP2E1\/E2-BDNF-miR132 Homeostasis Regulatory Network Is Region-Dependent in the Human Brain and Is Impaired in Rett Syndrome Patients. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00763"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1177\/088307389801300903","article-title":"Neurotrophic Factors in Cerebrospinal Fluid and Serum of Patients with Rett Syndrome","volume":"13","author":"Vanhala","year":"1998","journal-title":"J. Child Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.neuron.2005.12.027","article-title":"The Disease Progression of Mecp2 Mutant Mice Is Affected by the Level of BDNF Expression","volume":"49","author":"Chang","year":"2006","journal-title":"Neuron"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e19374","DOI":"10.7554\/eLife.19374","article-title":"Loss of MeCP2 Disrupts Cell Autonomous and Autocrine BDNF Signaling in Mouse Glutamatergic Neurons","volume":"5","author":"Sampathkumar","year":"2016","journal-title":"eLife"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.neuropharm.2013.03.024","article-title":"BDNF Deregulation in Rett Syndrome","volume":"76","author":"Li","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0896-6273(00)81010-7","article-title":"Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism","volume":"20","author":"Tao","year":"1998","journal-title":"Neuron"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Miyasaka, Y., and Yamamoto, N. (2021). Neuronal Activity Patterns Regulate Brain-Derived Neurotrophic Factor Expression in Cortical Cells via Neuronal Circuits. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.699583"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12877","DOI":"10.1523\/JNEUROSCI.2674-14.2014","article-title":"Cell-Type-Specific Repression by Methyl-CpG-Binding Protein 2 Is Biased toward Long Genes","volume":"34","author":"Sugino","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuroscience.2019.06.013","article-title":"Transcriptomic Studies in Mouse Models of Rett Syndrome: A Review","volume":"413","author":"Sanfeliu","year":"2019","journal-title":"Neuroscience"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"102821","DOI":"10.1016\/j.ceca.2023.102821","article-title":"Subcellular Localization and Transcriptional Regulation of Brain Ryanodine Receptors. Functional Implications","volume":"116","author":"Torres","year":"2023","journal-title":"Cell Calcium"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Rosado, J., Bui, V.D., Haas, C.A., Beck, J., Queisser, G., and Vlachos, A. (2022). Calcium Modeling of Spine Apparatus-Containing Human Dendritic Spines Demonstrates an \u201cAll-or-Nothing\u201d Communication Switch between the Spine Head and Dendrite. PLoS Comput. Biol., 18.","DOI":"10.1371\/journal.pcbi.1010069"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1073\/pnas.1013580108","article-title":"Involvement of Ryanodine Receptors in Neurotrophin-Induced Hippocampal Synaptic Plasticity and Spatial Memory Formation","volume":"108","author":"Adasme","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.neuropharm.2006.07.009","article-title":"Priming of Long-Term Potentiation Mediated by Ryanodine Receptor Activation in Rat Hippocampal Slices","volume":"52","author":"Mellentin","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9930962","DOI":"10.1155\/2021\/9930962","article-title":"Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3","volume":"2021","author":"Torres","year":"2021","journal-title":"Neural Plast."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bcp.2017.03.011","article-title":"Basal Ryanodine Receptor Activity Suppresses Autophagic Flux","volume":"132","author":"Vervliet","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.neuron.2020.10.005","article-title":"Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic Reticulum","volume":"109","author":"Kuijpers","year":"2021","journal-title":"Neuron"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1038\/s44321-024-00151-w","article-title":"Unraveling Autophagic Imbalances and Therapeutic Insights in Mecp2-Deficient Models","volume":"16","author":"Esposito","year":"2024","journal-title":"EMBO Mol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Denley, M.C.S., Gatford, N.J.F., Sellers, K.J., and Srivastava, D.P. (2018). Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00245"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Prokai-Tatrai, K., and Prokai, L. (2024). The Impact of 17\u03b2-Estradiol on the Estrogen-Deficient Female Brain: From Mechanisms to Therapy with Hot Flushes as Target Symptoms. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1310432"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1210\/en.2009-0955","article-title":"Epigenetic Regulation of Estrogen Receptor Alpha Gene Expression in the Mouse Cortex during Early Postnatal Development","volume":"151","author":"Westberry","year":"2010","journal-title":"Endocrinology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"6438","DOI":"10.1074\/jbc.M112.412478","article-title":"Post-Synaptic Density-95 (PSD-95) Binding Capacity of G-Protein-Coupled Receptor 30 (GPR30), an Estrogen Receptor That Can Be Identified in Hippocampal Dendritic Spines","volume":"288","author":"Akama","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13041-023-01003-3","article-title":"G-Protein Coupled Estrogen Receptor (GPER1) Activation Promotes Synaptic Insertion of AMPA Receptors and Induction of Chemical LTP at Hippocampal Temporoammonic-CA1 Synapses","volume":"16","author":"Clements","year":"2023","journal-title":"Mol. Brain"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kumar, A., and Foster, T.C. (2020). G Protein-Coupled Estrogen Receptor: Rapid Effects on Hippocampal-Dependent Spatial Memory and Synaptic Plasticity. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00385"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sanfeliu, A., Hokamp, K., Gill, M., and Tropea, D. (2019). Transcriptomic Analysis of Mecp2 Mutant Mice Reveals Differentially Expressed Genes and Altered Mechanisms in Both Blood and Brain. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00278"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Roque, C., Mendes-Oliveira, J., Duarte-Chendo, C., and Baltazar, G. (2019). The Role of G Protein-Coupled Estrogen Receptor 1 on Neurological Disorders. Front. Neuroendocrinol., 55.","DOI":"10.1016\/j.yfrne.2019.100786"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"15148","DOI":"10.1073\/pnas.0802379105","article-title":"Estrogens Directly Potentiate Neuronal L-Type Ca2+ Channels","volume":"105","author":"Sarkar","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"ENEURO.0475-21.2022","DOI":"10.1523\/ENEURO.0475-21.2022","article-title":"Differential Effects of the G-Protein-Coupled Estrogen Receptor (GPER) on Rat Embryonic (E18) Hippocampal and Cortical Neurons","volume":"9","author":"Pemberton","year":"2022","journal-title":"eNeuro"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Haase, F., Singh, R., Gloss, B., Tam, P., and Gold, W. (2022). Meta-Analysis Identifies BDNF and Novel Common Genes Differently Altered in Cross-Species Models of Rett Syndrome. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202207.0030.v1"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Indelicato, E., and Boesch, S. (2021). From Genotype to Phenotype: Expanding the Clinical Spectrum of CACNA1A Variants in the Era of Next Generation Sequencing. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.639994"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1177\/0883073818754987","article-title":"An Atypical Rett Syndrome Phenotype Due to a Novel Missense Mutation in CACNA1A","volume":"33","author":"Epperson","year":"2018","journal-title":"J. Child Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Liedtke, W.B., and Heller, S. (2007). TRPV1 Receptors and Signal Transduction. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades, CRC Press\/Taylor & Francis. Frontiers in Neuroscience.","DOI":"10.1201\/9781420005844"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1744806916633206","DOI":"10.1177\/1744806916633206","article-title":"Regulation of Transient Receptor Potential Vanilloid 1 Expression in Trigeminal Ganglion Neurons via Methyl-CpG Binding Protein 2 Signaling Contributes Tongue Heat Sensitivity and Inflammatory Hyperalgesia in Mice","volume":"12","author":"Suzuki","year":"2016","journal-title":"Mol. Pain."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eaau0164","DOI":"10.1126\/scitranslmed.aau0164","article-title":"Pharmacological Enhancement of KCC2 Gene Expression Exerts Therapeutic Effects on Human Rett Syndrome Neurons and Mecp2 Mutant Mice","volume":"11","author":"Tang","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Meza, R.C., Ancat\u00e9n-Gonz\u00e1lez, C., Chiu, C.Q., and Ch\u00e1vez, A.E. (2022). Transient Receptor Potential Vanilloid 1 Function at Central Synapses in Health and Disease. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.864828"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"eadq3374","DOI":"10.1126\/sciadv.adq3374","article-title":"A Genetically Encoded Actuator Boosts L-Type Calcium Channel Function in Diverse Physiological Settings","volume":"10","author":"Morfin","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"eadd4666","DOI":"10.1126\/scitranslmed.add4666","article-title":"Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons","volume":"15","author":"Qian","year":"2023","journal-title":"Sci. Transl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10490\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:17:48Z","timestamp":1761729468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":120,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110490"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110490","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}