دورية أكاديمية
أعرض في EDS

Treatment with the Bacterial Toxin CNF1 Selectively Rescues Cognitive and Brain Mitochondrial Deficits in a Female Mouse Model of Rett Syndrome Carrying a MeCP2-Null Mutation.

التفاصيل البيبلوغرافية
العنوان: Treatment with the Bacterial Toxin CNF1 Selectively Rescues Cognitive and Brain Mitochondrial Deficits in a Female Mouse Model of Rett Syndrome Carrying a MeCP2-Null Mutation.
المؤلفون: Urbinati C; Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy., Cosentino L; Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy., Germinario EAP; Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, 00161 Rome, Italy., Valenti D; Bioenergetics and Molecular Biotechnologies, Institute of Biomembranes, National Council of Research, 70126 Bari, Italy., Vigli D; Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy., Ricceri L; Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy., Laviola G; Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy., Fiorentini C; Association for Research on Integrative Oncology Therapies (ARTOI), 00165 Rome, Italy., Vacca RA; Bioenergetics and Molecular Biotechnologies, Institute of Biomembranes, National Council of Research, 70126 Bari, Italy., Fabbri A; Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, 00161 Rome, Italy., De Filippis B; Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2021 Jun 23; Vol. 22 (13). Date of Electronic Publication: 2021 Jun 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Bacterial Toxins/*pharmacology , Brain/*drug effects , Escherichia coli Proteins/*pharmacology , Methyl-CpG-Binding Protein 2/*genetics , Mitochondria/*drug effects , Rett Syndrome/*drug therapy, Animals ; Bacterial Toxins/administration & dosage ; Brain/metabolism ; Disease Models, Animal ; Escherichia coli Proteins/administration & dosage ; Fear/drug effects ; Female ; Infusions, Intraventricular ; Loss of Function Mutation ; Memory Disorders/drug therapy ; Memory Disorders/etiology ; Mice, Mutant Strains ; Microfilament Proteins/metabolism ; Mitochondria/metabolism ; Nerve Tissue Proteins/metabolism ; Rett Syndrome/etiology ; TOR Serine-Threonine Kinases/metabolism ; Mice
مستخلص: Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene and a major cause of intellectual disability in females. No cure exists for RTT. We previously reported that the behavioural phenotype and brain mitochondria dysfunction are widely rescued by a single intracerebroventricular injection of the bacterial toxin CNF1 in a RTT mouse model carrying a truncating mutation of the MeCP2 gene (MeCP2-308 mice). Given the heterogeneity of MECP2 mutations in RTT patients, we tested the CNF1 therapeutic efficacy in a mouse model carrying a null mutation (MeCP2-Bird mice). CNF1 selectively rescued cognitive defects, without improving other RTT-related behavioural alterations, and restored brain mitochondrial respiratory chain complex activity in MeCP2-Bird mice. To shed light on the molecular mechanisms underlying the differential CNF1 effects on the behavioural phenotype, we compared treatment effects on relevant signalling cascades in the brain of the two RTT models. CNF1 provided a significant boost of the mTOR activation in MeCP2-308 hippocampus, which was not observed in the MeCP2-Bird model, possibly explaining the differential effects of CNF1. These results demonstrate that CNF1 efficacy depends on the mutation beared by MeCP2-mutated mice, stressing the need of testing potential therapeutic approaches across RTT models.
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معلومات مُعتمدة: #3107 International Rett syndrome Foundation (USA); #GR-2018-12366210 Italian Ministry of Health (Italy); (no number) Jerome Lejeune Foundation (France)
فهرسة مساهمة: Keywords: Rett syndrome; Rho GTPases; behaviour; cognition; energy metabolism; mTOR; mitochondria; mouse models
المشرفين على المادة: 0 (Bacterial Toxins)
0 (Escherichia coli Proteins)
0 (Mecp2 protein, mouse)
0 (Methyl-CpG-Binding Protein 2)
0 (Microfilament Proteins)
0 (Nerve Tissue Proteins)
0 (neurabin)
106803-33-2 (cytotoxic necrotizing factor type 1)
EC 2.7.1.1 (mTOR protein, mouse)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20210702 Date Completed: 20210804 Latest Revision: 20240821
رمز التحديث: 20240821
مُعرف محوري في PubMed: PMC8269120
DOI: 10.3390/ijms22136739
PMID: 34201747
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms22136739