{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:47:49Z","timestamp":1763142469917,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondecyt","award":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"],"award-info":[{"award-number":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"]}]},{"name":"Fondecyt Postdoctorado","award":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"],"award-info":[{"award-number":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"]}]},{"name":"Anillo","award":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"],"award-info":[{"award-number":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"]}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Doctorados, Universidad San Sebasti\u00e1n (DLL)","award":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"],"award-info":[{"award-number":["1181574","1230905","3180518","11230898","1221213","3210493","ACT210039","USS-FIN-23-FAPE-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Classical Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene, resulting in a devastating phenotype associated with a lack of gene expression control. Mouse models lacking Mecp2 expression with an RTT-like phenotype have been developed to advance therapeutic alternatives. Environmental enrichment (EE) attenuates RTT symptoms in patients and mouse models. However, the mechanisms underlying the effects of EE on RTT have not been fully elucidated. We housed male hemizygous Mecp2-null (Mecp2-\/y) and wild-type mice in specially conditioned cages to enhance sensory, cognitive, social, and motor stimulation. EE attenuated the progression of the RTT phenotype by preserving neuronal cytoarchitecture and neural plasticity markers. Furthermore, EE ameliorated defects in neuromuscular junction organization and restored the motor deficit of Mecp2-\/y mice. Treatment with plasma from young WT mice was used to assess whether the increased activity could modify plasma components, mimicking the benefits of EE in Mecp2-\/y. Plasma treatment attenuated the RTT phenotype by improving neurological markers, suggesting that peripheral signals of mice with normal motor function have the potential to reactivate dormant neurodevelopment in RTT mice. These findings demonstrate how EE and treatment with young plasma ameliorate RTT-like phenotype in mice, opening new therapeutical approaches for RTT patients.<\/jats:p>","DOI":"10.3390\/biom15050748","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:44:57Z","timestamp":1747813497000},"page":"748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-5896","authenticated-orcid":false,"given":"Sof\u00eda","family":"Espinoza","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Providencia, Santiago 7510157, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Navia","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs), Valdivia 5110466, Chile"},{"name":"Facultad de Medicina, Universidad Austral de Chile, Valdivia 5091000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-2920","authenticated-orcid":false,"given":"Rodrigo F.","family":"Torres","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs), Valdivia 5110466, Chile"},{"name":"Departamento de Ciencias B\u00e1sicas, Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Puerto Montt 5501842, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-0806","authenticated-orcid":false,"given":"Nuria","family":"Llontop","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Providencia, Santiago 7510157, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Valladares","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Providencia, Santiago 7510157, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9882-921X","authenticated-orcid":false,"given":"Cristina","family":"Silva","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Providencia, Santiago 7510157, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Vivero","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad 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5110466, Chile"},{"name":"Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5091000, Chile"},{"name":"Departamento de Ciencias Biol\u00f3gicas y Qu\u00edmicas, Facultad de Ciencias, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4080870, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5493-7212","authenticated-orcid":false,"given":"Patricia","family":"Ojeda-Provoste","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs), Valdivia 5110466, Chile"},{"name":"Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5091000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Pineda","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs), Valdivia 5110466, Chile"},{"name":"Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5091000, 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Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4070386, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-8726","authenticated-orcid":false,"given":"Bredford","family":"Kerr","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Providencia, Santiago 7510157, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","first-page":"723","article-title":"Uber Ein Eigenartiges Hirnatrophisches Syndrom Bei Hyperammonaemie in Kindesalter","volume":"116","author":"Rett","year":"1966","journal-title":"Wien. 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