Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model
Classical Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the <i>MECP2</i> gene, resulting in a devastating phenotype associated with a lack of gene expression control. Mouse models lacking <i>Mecp2</i> expression with an RTT-like phenotype have be...
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2025-05-01
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| author | Sofía Espinoza Camila Navia Rodrigo F. Torres Nuria Llontop Verónica Valladares Cristina Silva Ariel Vivero Exequiel Novoa-Padilla Jessica Soto-Covasich Jessica Mella Ricardo Kouro Sharin Valdivia Marco Pérez-Bustamante Patricia Ojeda-Provoste Nancy Pineda Sonja Buvinic Dasfne Lee-Liu Juan Pablo Henríquez Bredford Kerr |
| author_facet | Sofía Espinoza Camila Navia Rodrigo F. Torres Nuria Llontop Verónica Valladares Cristina Silva Ariel Vivero Exequiel Novoa-Padilla Jessica Soto-Covasich Jessica Mella Ricardo Kouro Sharin Valdivia Marco Pérez-Bustamante Patricia Ojeda-Provoste Nancy Pineda Sonja Buvinic Dasfne Lee-Liu Juan Pablo Henríquez Bredford Kerr |
| author_sort | Sofía Espinoza |
| collection | DOAJ |
| description | Classical Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the <i>MECP2</i> gene, resulting in a devastating phenotype associated with a lack of gene expression control. Mouse models lacking <i>Mecp2</i> 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 <i>Mecp2</i>-null (<i>Mecp2<sup>-/y</sup></i>) 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 <i>Mecp2<sup>-/y</sup></i> 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 <i>Mecp2<sup>-/y</sup></i>. 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. |
| format | Article |
| id | doaj-art-f12f50f7cdda495eb72bcf3e7f9d7b9a |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-f12f50f7cdda495eb72bcf3e7f9d7b9a2025-08-20T03:47:53ZengMDPI AGBiomolecules2218-273X2025-05-0115574810.3390/biom15050748Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse ModelSofía Espinoza0Camila Navia1Rodrigo F. Torres2Nuria Llontop3Verónica Valladares4Cristina Silva5Ariel Vivero6Exequiel Novoa-Padilla7Jessica Soto-Covasich8Jessica Mella9Ricardo Kouro10Sharin Valdivia11Marco Pérez-Bustamante12Patricia Ojeda-Provoste13Nancy Pineda14Sonja Buvinic15Dasfne Lee-Liu16Juan Pablo Henríquez17Bredford Kerr18Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Providencia, Santiago 7510157, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Providencia, Santiago 7510157, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Providencia, Santiago 7510157, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Providencia, Santiago 7510157, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Providencia, Santiago 7510157, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileNeuromuscular Studies Laboratory (NeSt Lab), Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia 5091000, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileCentro de Estudios Científicos (CECs), Valdivia 5110466, ChileFacultad de Odontología, Universidad de Chile, Santiago 8380000, ChileEscuela de Química y Farmacia, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago 7510157, ChileNeuromuscular Studies Laboratory (NeSt Lab), Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia 5091000, ChileCentro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Providencia, Santiago 7510157, ChileClassical Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the <i>MECP2</i> gene, resulting in a devastating phenotype associated with a lack of gene expression control. Mouse models lacking <i>Mecp2</i> 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 <i>Mecp2</i>-null (<i>Mecp2<sup>-/y</sup></i>) 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 <i>Mecp2<sup>-/y</sup></i> 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 <i>Mecp2<sup>-/y</sup></i>. 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.https://www.mdpi.com/2218-273X/15/5/748Rett syndrome<i>Mecp2</i>environmental enrichmentplasma treatment |
| spellingShingle | Sofía Espinoza Camila Navia Rodrigo F. Torres Nuria Llontop Verónica Valladares Cristina Silva Ariel Vivero Exequiel Novoa-Padilla Jessica Soto-Covasich Jessica Mella Ricardo Kouro Sharin Valdivia Marco Pérez-Bustamante Patricia Ojeda-Provoste Nancy Pineda Sonja Buvinic Dasfne Lee-Liu Juan Pablo Henríquez Bredford Kerr Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model Biomolecules Rett syndrome <i>Mecp2</i> environmental enrichment plasma treatment |
| title | Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model |
| title_full | Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model |
| title_fullStr | Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model |
| title_full_unstemmed | Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model |
| title_short | Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model |
| title_sort | neuronal plasticity dependent paradigm and young plasma treatment prevent synaptic and motor deficit in a rett syndrome mouse model |
| topic | Rett syndrome <i>Mecp2</i> environmental enrichment plasma treatment |
| url | https://www.mdpi.com/2218-273X/15/5/748 |
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