دورية أكاديمية
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.
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. |
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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. |
References: | Neuron. 2002 Jul 18;35(2):243-54. (PMID: 12160743) Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):636-41. (PMID: 17202256) Behav Pharmacol. 2008 Sep;19(5-6):501-17. (PMID: 18690105) Neuropharmacology. 2013 May;68:106-15. (PMID: 22940001) Hum Mol Genet. 2013 Jan 1;22(1):96-109. (PMID: 23026749) Free Radic Biol Med. 2015 Jun;83:167-77. (PMID: 25708779) Neuropsychopharmacology. 2012 Apr;37(5):1152-63. (PMID: 22157810) Neural Plast. 2015;2015:326184. (PMID: 26185689) Neuropsychopharmacology. 2014 Oct;39(11):2506-18. (PMID: 24809912) Neuron. 2007 Nov 8;56(3):422-37. (PMID: 17988628) Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:202-17. (PMID: 24548784) Int J Mol Sci. 2021 Mar 30;22(7):. (PMID: 33808109) J Psychopharmacol. 2019 Jul;33(7):894-907. (PMID: 31084246) PLoS One. 2013 May 30;8(5):e65898. (PMID: 23738020) Hum Mol Genet. 2011 Mar 15;20(6):1182-96. (PMID: 21212100) PLoS One. 2015 Oct 12;10(10):e0140495. (PMID: 26457896) Prog Neurobiol. 2012 Feb;96(2):268-82. (PMID: 22285767) Int Rev Neurobiol. 2009;89:147-60. (PMID: 19900619) Hum Mol Genet. 2005 Jan 15;14(2):205-20. (PMID: 15548546) J Neurosci. 2011 Oct 19;31(42):15163-72. (PMID: 22016550) Mitochondrion. 2014 Mar;15:10-7. (PMID: 24613463) Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9941-6. (PMID: 24958891) Biochem Soc Trans. 2010 Apr;38(2):498-506. (PMID: 20298210) Front Neurosci. 2020 Jan 29;14:20. (PMID: 32063830) Cell Stem Cell. 2013 Oct 3;13(4):446-58. (PMID: 24094325) BMB Rep. 2018 Nov;51(11):549-556. (PMID: 30269744) Nat Genet. 2001 Mar;27(3):322-6. (PMID: 11242117) Neurobiol Dis. 2016 Jun;90:75-85. (PMID: 26284893) Mol Microbiol. 1993 Sep;9(6):1247-54. (PMID: 7934938) Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2029-34. (PMID: 19208815) Front Cell Neurosci. 2017 Mar 14;11:58. (PMID: 28352216) Cell. 2017 Mar 9;168(6):960-976. (PMID: 28283069) Nat Struct Mol Biol. 2004 Feb;11(2):113-4. (PMID: 14749770) Psychopharmacology (Berl). 2001 Jul;156(2-3):194-215. (PMID: 11549223) Cell Rep. 2015 Sep 22;12(11):1887-901. (PMID: 26344767) Dev Dyn. 2018 Jan;247(1):47-53. (PMID: 28643345) Eur Neuropsychopharmacol. 2015 Jun;25(6):889-901. (PMID: 25890884) Genes Brain Behav. 2010 Mar 1;9(2):213-23. (PMID: 19958389) Neuropharmacology. 2018 Sep 15;140:121-129. (PMID: 30056123) Nat Protoc. 2006;1(3):1117-9. (PMID: 17406392) Behav Brain Res. 2010 Sep 1;212(1):78-83. (PMID: 20362628) Mamm Genome. 2019 Jun;30(5-6):90-110. (PMID: 30820643) J Biol Chem. 1998 May 29;273(22):13669-74. (PMID: 9593707) Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9287-92. (PMID: 10922077) Neurosci Biobehav Rev. 2019 Dec;107:115-135. (PMID: 31108160) Dis Model Mech. 2012 Nov;5(6):733-45. (PMID: 23115203) Nat Rev Neurosci. 2018 Jun;19(6):368-382. (PMID: 29740174) Curr Top Behav Neurosci. 2012;12:251-318. (PMID: 22367921) Cell. 2010 Nov 12;143(4):527-39. (PMID: 21074045) Anal Biochem. 2014 Jan 1;444:25-31. (PMID: 24018341) J Clin Med. 2020 Jun 01;9(6):. (PMID: 32492904) Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:285-301. (PMID: 24971827) Neuropharmacology. 2017 Jul 15;121:79-88. (PMID: 28419872) Neuropharmacology. 2019 Jan;144:104-114. (PMID: 30326240) Int J Mol Sci. 2018 Jun 21;19(7):. (PMID: 29933571) |
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 |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms22136739 |