Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome
Rett syndrome (RTT, online MIM 312750) is a devastating neurodevelopmental disorder characterized by motor and cognitive disabilities. It is mainly caused by pathogenetic variants in the X-linked <i>MECP2</i> gene, encoding an epigenetic factor crucial for brain functioning. Despite inte...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/4/606 |
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| author | Giuseppe Pepe Salvatore Fioriniello Federico Marracino Luca Capocci Vittorio Maglione Maurizio D’Esposito Alba Di Pardo Floriana Della Ragione |
| author_facet | Giuseppe Pepe Salvatore Fioriniello Federico Marracino Luca Capocci Vittorio Maglione Maurizio D’Esposito Alba Di Pardo Floriana Della Ragione |
| author_sort | Giuseppe Pepe |
| collection | DOAJ |
| description | Rett syndrome (RTT, online MIM 312750) is a devastating neurodevelopmental disorder characterized by motor and cognitive disabilities. It is mainly caused by pathogenetic variants in the X-linked <i>MECP2</i> gene, encoding an epigenetic factor crucial for brain functioning. Despite intensive studies, the RTT pathogenetic mechanism remains to be fully elucidated. Impaired vascular function has been previously reported in RTT mouse models; however, whether an altered brain vascular homeostasis and the subsequent blood–brain barrier (BBB) breakdown occur in RTT and contribute to the disease-related cognitive impairment is still unknown. Interestingly, in symptomatic <i>Mecp2</i>-null (<i>Mecp2</i><sup>-/y</sup><i>, Mecp2</i><sup>tm1.1Bird</sup>) mice, we found enhanced BBB permeability associated with an aberrant expression of the tight junction proteins <i>Ocln</i> and <i>Cldn</i>-5 in different brain areas, in terms of both transcript and protein levels. Additionally, <i>Mecp2</i>-null mice showed an altered expression of different genes encoding factors with a role in the BBB structure and function, such as <i>Cldn3</i>, <i>Cldn12</i>, <i>Mpdz</i>, <i>Jam2</i>, and <i>Aqp4</i>. With this study, we provide the first evidence of impaired BBB integrity in RTT and highlight a potential new molecular hallmark of the disease that might open new perspectives for the setting-up of novel therapeutic strategies. |
| first_indexed | 2024-03-11T05:12:34Z |
| format | Article |
| id | doaj.art-f8b13bb92ed44651b12c02824c1dd910 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T05:12:34Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f8b13bb92ed44651b12c02824c1dd9102023-11-17T18:28:50ZengMDPI AGBiomolecules2218-273X2023-03-0113460610.3390/biom13040606Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett SyndromeGiuseppe Pepe0Salvatore Fioriniello1Federico Marracino2Luca Capocci3Vittorio Maglione4Maurizio D’Esposito5Alba Di Pardo6Floriana Della Ragione7IRCCS Neuromed, 86077 Pozzilli, ItalyInstitute of Genetics and Biophysics ‘A. Buzzati-Traverso’, CNR, 80131 Naples, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyRett syndrome (RTT, online MIM 312750) is a devastating neurodevelopmental disorder characterized by motor and cognitive disabilities. It is mainly caused by pathogenetic variants in the X-linked <i>MECP2</i> gene, encoding an epigenetic factor crucial for brain functioning. Despite intensive studies, the RTT pathogenetic mechanism remains to be fully elucidated. Impaired vascular function has been previously reported in RTT mouse models; however, whether an altered brain vascular homeostasis and the subsequent blood–brain barrier (BBB) breakdown occur in RTT and contribute to the disease-related cognitive impairment is still unknown. Interestingly, in symptomatic <i>Mecp2</i>-null (<i>Mecp2</i><sup>-/y</sup><i>, Mecp2</i><sup>tm1.1Bird</sup>) mice, we found enhanced BBB permeability associated with an aberrant expression of the tight junction proteins <i>Ocln</i> and <i>Cldn</i>-5 in different brain areas, in terms of both transcript and protein levels. Additionally, <i>Mecp2</i>-null mice showed an altered expression of different genes encoding factors with a role in the BBB structure and function, such as <i>Cldn3</i>, <i>Cldn12</i>, <i>Mpdz</i>, <i>Jam2</i>, and <i>Aqp4</i>. With this study, we provide the first evidence of impaired BBB integrity in RTT and highlight a potential new molecular hallmark of the disease that might open new perspectives for the setting-up of novel therapeutic strategies.https://www.mdpi.com/2218-273X/13/4/606Rett syndromeblood–brain barrierMeCP2neurodevelopmental disorderautism spectrum disorder |
| spellingShingle | Giuseppe Pepe Salvatore Fioriniello Federico Marracino Luca Capocci Vittorio Maglione Maurizio D’Esposito Alba Di Pardo Floriana Della Ragione Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome Biomolecules Rett syndrome blood–brain barrier MeCP2 neurodevelopmental disorder autism spectrum disorder |
| title | Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome |
| title_full | Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome |
| title_fullStr | Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome |
| title_full_unstemmed | Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome |
| title_short | Blood–Brain Barrier Integrity Is Perturbed in a <i>Mecp2</i>-Null Mouse Model of Rett Syndrome |
| title_sort | blood brain barrier integrity is perturbed in a i mecp2 i null mouse model of rett syndrome |
| topic | Rett syndrome blood–brain barrier MeCP2 neurodevelopmental disorder autism spectrum disorder |
| url | https://www.mdpi.com/2218-273X/13/4/606 |
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