دورية أكاديمية
Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome
| العنوان: | Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome |
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| المؤلفون: | Musokhranova, Uliana, Grau, Cristina, Vergara, Cristina, Rodríguez-Pascau, Laura, Xiol, Clara, Castells, Alba A, Alcántara, Soledad, Rodríguez-Pombo, Pilar, Pizcueta, Pilar, Martinell, Marc, García-Cazorla, Angels, Oyarzábal, Alfonso |
| المساهمون: | Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, Mi Princesa Rett |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | Background: Rett syndrome is a neuropediatric disease occurring due to mutations in MECP2 and characterized by a regression in the neuronal development following a normal postnatal growth, which results in the loss of acquired capabilities such as speech or purposeful usage of hands. While altered neurotransmission and brain development are the center of its pathophysiology, alterations in mitochondrial performance have been previously outlined, shaping it as an attractive target for the disease treatment. Methods: We have thoroughly described mitochondrial performance in two Rett models, patients’ primary fibroblasts and female Mecp2 mice brain, discriminating between different brain areas. The characterization was made according to their bioenergetics function, oxidative stress, network dynamics or ultrastructure. Building on that, we have studied the effect of leriglitazone, a PPARγ agonist, in the modulation of mitochondrial performance. For that, we treated Rett female mice with 75 mg/kg/day leriglitazone from weaning until sacrifice at 7 months, studying both the mitochondrial performance changes and their consequences on the mice phenotype. Finally, we studied its effect on neuroinflammation based on the presence of reactive glia by immunohistochemistry and through a cytokine panel. Results: We have described mitochondrial alterations in Rett fibroblasts regarding both shape and bioenergetic functions, as they displayed less interconnected and shorter mitochondria and reduced ATP production along with increased oxidative stress. The bioenergetic alterations were recalled in Rett mice models, being especially significant in cerebellum, already detectable in pre-symptomatic stages. Treatment with leriglitazone recovered the bioenergetic alterations both in Rett fibroblasts and female mice and exerted an anti-inflammatory effect in the latest, resulting in the amelioration of the mice phenotype both in general condition and exploratory activity. Conclusions: Our studies confirm the mitochondrial dysfunction ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 1479-5876 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115748RB-I00/ES/MODELADO DEL CONTROL AMBIENTAL DE LA DIFERENCIACION DE LOS PROGENITORES NEURALES: UN PUNTO DE ENCUENTRO ENTRE LOS TRASTORNOS DEL DESARROLLO Y LA REGENERACION NEURAL/; info:eu-repo/grantAgreement/Generalitat de Catalunya “PIF-Salut” Grant PFP00201-PERIS (UM, AGC, AO); info:eu-repo/grantAgreement/Princesa Rett and Rettando al Síndrome de Rett donations (AGC, AO, UM, CG, CX); Publisher's version; http://dx.doi.org/10.1186/s12967-023-04622-5Test; Sí; Journal of Translational Medicine 21 (2023); http://hdl.handle.net/10261/357526Test; http://dx.doi.org/10.13039/501100011033Test; http://dx.doi.org/10.13039/501100002809Test; http://dx.doi.org/10.13039/501100004837Test |
| DOI: | 10.1186/s12967-023-04622-5 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100002809 |
| DOI: | 10.13039/501100004837 |
| الإتاحة: | https://doi.org/10.1186/s12967-023-04622-510.13039/50110001103310.13039/50110000280910.13039/501100004837Test http://hdl.handle.net/10261/357526Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.DD457CE5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14795876 |
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| DOI: | 10.1186/s12967-023-04622-5 |