دورية أكاديمية
أعرض في EDS

Reduced axonal caliber and structural changes in a rat model of Fragile X syndrome with a deletion of a K-Homology domain of Fmr1.

التفاصيل البيبلوغرافية
العنوان: Reduced axonal caliber and structural changes in a rat model of Fragile X syndrome with a deletion of a K-Homology domain of Fmr1.
المؤلفون: Golden CEM; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Yee Y; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.; Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada., Wang VX; BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Harony-Nicolas H; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Hof PR; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Lerch JP; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.; Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada.; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK., Buxbaum JD; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.
المصدر: Translational psychiatry [Transl Psychiatry] 2020 Aug 12; Vol. 10 (1), pp. 280. Date of Electronic Publication: 2020 Aug 12.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101562664 Publication Model: Electronic Cited Medium: Internet ISSN: 2158-3188 (Electronic) Linking ISSN: 21583188 NLM ISO Abbreviation: Transl Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Group
مواضيع طبية MeSH: Fragile X Syndrome*/genetics, Animals ; Axons ; Brain/metabolism ; Corpus Callosum ; Female ; Fragile X Mental Retardation Protein/genetics ; Male ; Rats
مستخلص: Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene. Neuroanatomical alterations have been reported in both male and female individuals with FXS, yet the morphological underpinnings of these alterations have not been elucidated. In the current study, we found structural changes in both male and female rats that model FXS, some of which are similarly impaired in both sexes, including the superior colliculus and periaqueductal gray, and others that show sex-specific changes. The splenium of the corpus callosum, for example, was only impaired in males. We also found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Furthermore, we found that overall, male rats have higher brain-wide diffusion than female rats. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and reveal an impairment at the level of the axon that could cause structural changes in white matter regions.
References: Bagni, C., Tassone, F., Neri, G. & Hagerman, R. Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics. J. Clin. Invest 122, 4314–4322 (2012). (PMID: 23202739353353910.1172/JCI63141)
Hagerman, R. J. et al. Fragile X syndrome. Nat. Rev. Dis. Prim. 3, 17065 (2017). (PMID: 2896018410.1038/nrdp.2017.65)
Bray, S. et al. Aberrant frontal lobe maturation in adolescents with fragile X syndrome is related to delayed cognitive maturation. Biol. Psychiatry 70, 852–858 (2011). (PMID: 21802660319129910.1016/j.biopsych.2011.05.038)
Villalon-Reina, J. et al. White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging. Neuroimage 81, 441–454 (2013). (PMID: 10.1016/j.neuroimage.2013.04.02823602925)
Lai, J. K., Lerch, J. P., Doering, L. C., Foster, J. A. & Ellegood, J. Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain. Neuroscience 318, 12–21 (2016). (PMID: 2679459110.1016/j.neuroscience.2016.01.021)
Kay, R. B., Gabreski, N. A. & Triplett, J. W. Visual subcircuit-specific dysfunction and input-specific mispatterning in the superior colliculus of fragile X mice. J. Neurodev. Disord. 10, 23 (2018). (PMID: 29950161602270010.1186/s11689-018-9241-1)
Haberl, M. G. et al. Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism. Sci. Adv. 1, e1500775 (2015). (PMID: 26702437468132510.1126/sciadv.1500775)
Hall, S. S., Jiang, H., Reiss, A. L. & Greicius, M. D. Identifying large-scale brain networks in fragile X syndrome. JAMA Psychiatry 70, 1215–1223 (2013). (PMID: 24068330404026610.1001/jamapsychiatry.2013.247)
Zerbi, V. et al. Inhibiting mGluR5 activity by AFQ056/Mavoglurant rescues circuit-specific functional connectivity in Fmr1 knockout mice. Neuroimage 191, 392–402 (2019). (PMID: 3080782010.1016/j.neuroimage.2019.02.051)
Richter, J. D., Bassell, G. J. & Klann, E. Dysregulation and restoration of translational homeostasis in fragile X syndrome. Nat. Rev. Neurosci. 16, 595–605 (2015). (PMID: 26350240468889610.1038/nrn4001)
Golden, C. E. M. et al. Deletion of the KH1 domain of Fmr1 leads to transcriptional alterations and attentional deficits in rats. Cereb. Cortex 29, 2228–2244 (2019). (PMID: 30877790645891510.1093/cercor/bhz029)
Engineer, C. T. et al. Degraded speech sound processing in a rat model of fragile X syndrome. Brain Res. 1564, 72–84 (2014). (PMID: 24713347403446910.1016/j.brainres.2014.03.049)
Radyushkin, K. et al. Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav. 8, 416–425 (2009). (PMID: 1924344810.1111/j.1601-183X.2009.00487.x)
Budin, F. et al. Fully automated rodent brain MR image processing pipeline on a Midas server: from acquired images to region-based statistics. Front. Neuroinform. 7, 15 (2013). (PMID: 23964234374153510.3389/fninf.2013.00015)
Yushkevich, P. A. et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 31, 1116–1128 (2006). (PMID: 1654596510.1016/j.neuroimage.2006.01.015)
Lerch, J. P., Sled, J. G. & Henkelman, R. M. MRI phenotyping of genetically altered mice. Methods Mol. Biol. 711, 349–361 (2011). (PMID: 2127961110.1007/978-1-61737-992-5_17)
Avants, B. B. et al. The Insight ToolKit image registration framework. Front. Neuroinform. 8, 44 (2014). (PMID: 24817849400942510.3389/fninf.2014.00044)
Papp, E. A., Leergaard, T. B., Calabrese, E., Johnson, G. A. & Bjaalie, J. G. Waxholm Space atlas of the Sprague Dawley rat brain. Neuroimage 97, 374–386 (2014). (PMID: 2472633610.1016/j.neuroimage.2014.04.001)
Kjonigsen, L. J., Lillehaug, S., Bjaalie, J. G., Witter, M. P. & Leergaard, T. B. Waxholm Space atlas of the rat brain hippocampal region: three-dimensional delineations based on magnetic resonance and diffusion tensor imaging. Neuroimage 108, 441–449 (2015). (PMID: 2558502210.1016/j.neuroimage.2014.12.080)
Spring, S., Lerch, J. P. & Henkelman, R. M. Sexual dimorphism revealed in the structure of the mouse brain using three-dimensional magnetic resonance imaging. Neuroimage 35, 1424–1433 (2007). (PMID: 1740897110.1016/j.neuroimage.2007.02.023)
Zorio, D. A., Jackson, C. M., Liu, Y., Rubel, E. W. & Wang, Y. Cellular distribution of the fragile X mental retardation protein in the mouse brain. J. Comp. Neurol. 525, 818–849 (2017). (PMID: 2753953510.1002/cne.24100)
Winklewski, P. J. et al. Understanding the physiopathology behind axial and radial diffusivity changes-what do we know? Front. Neurol. 9, 92 (2018). (PMID: 29535676583508510.3389/fneur.2018.00092)
Klawiter, E. C. et al. Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords. Neuroimage 55, 1454–1460 (2011). (PMID: 2123859710.1016/j.neuroimage.2011.01.007)
van Hemmen, J. et al. Sex differences in white matter microstructure in the human brain predominantly reflect differences in sex hormone exposure. Cereb. Cortex 27, 2994–3001 (2017). (PMID: 27226438)
Ingalhalikar, M. et al. Sex differences in the structural connectome of the human brain. Proc. Natl Acad. Sci. USA 111, 823–828 (2014). (PMID: 2429790410.1073/pnas.1316909110)
Hoeft, F. et al. Morphometric spatial patterns differentiating boys with fragile X syndrome, typically developing boys, and developmentally delayed boys aged 1 to 3 years. Arch. Gen. Psychiatry 65, 1087–1097 (2008). (PMID: 18762595286440010.1001/archpsyc.65.9.1087)
Hagerman, R., Lauterborn, J., Au, J. & Berry-Kravis, E. Fragile X syndrome and targeted treatment trials. Results Probl. Cell Differ. 54, 297–335 (2012). (PMID: 22009360411477510.1007/978-3-642-21649-7_17)
Ofori, E. et al. Free water improves detection of changes in the substantia nigra in parkinsonism: a multisite study. Mov. Disord. 32, 1457–1464 (2017). (PMID: 28714593571804610.1002/mds.27100)
Paul, K., Venkitaramani, D. V. & Cox, C. L. Dampened dopamine-mediated neuromodulation in prefrontal cortex of fragile X mice. J. Physiol. 591, 1133–1143 (2013). (PMID: 2314831610.1113/jphysiol.2012.241067)
Krauzlis, R. J., Lovejoy, L. P. & Zenon, A. Superior colliculus and visual spatial attention. Annu Rev. Neurosci. 36, 165–182 (2013). (PMID: 2368265910.1146/annurev-neuro-062012-170249)
Tolomeo, S., Gray, S., Matthews, K., Steele, J. D. & Baldacchino, A. Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence. Psychol. Med. 46, 2841–2853 (2016). (PMID: 2745223810.1017/S0033291716001513)
Fall, S., Querne, L., Le Moing, A. G. & Berquin, P. Individual differences in subcortical microstructure organization reflect reaction time performances during a flanker task: a diffusion tensor imaging study in children with and without ADHD. Psychiatry Res. 233, 50–56 (2015). (PMID: 2602501310.1016/j.pscychresns.2015.05.001)
Qiu, M. G. et al. Changes of brain structure and function in ADHD children. Brain Topogr. 24, 243–252 (2011). (PMID: 2119180710.1007/s10548-010-0168-4)
Chen, L. et al. A systematic review and meta-analysis of tract-based spatial statistics studies regarding attention-deficit/hyperactivity disorder. Neurosci. Biobehav Rev. 68, 838–847 (2016). (PMID: 2745058210.1016/j.neubiorev.2016.07.022)
Golden, C. E., Buxbaum, J. D. & De Rubeis, S. Disrupted circuits in mouse models of autism spectrum disorder and intellectual disability. Curr. Opin. Neurobiol. 48, 106–112 (2018). (PMID: 2922298910.1016/j.conb.2017.11.006)
Bodaleo, F., Tapia-Monsalves, C., Cea-Del Rio, C., Gonzalez-Billault, C. & Nunez-Parra, A. Structural and functional abnormalities in the olfactory system of fragile X syndrome models. Front Mol. Neurosci. 12, 135 (2019). (PMID: 31191246654805810.3389/fnmol.2019.00135)
Goebel-Goody, S. M. et al. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain Behav. 11, 586–600 (2012). (PMID: 22405502392213110.1111/j.1601-183X.2012.00781.x)
Chen, L. & Toth, M. Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience 103, 1043–1050 (2001). (PMID: 1130121110.1016/S0306-4522(01)00036-7)
Zerbi, V. et al. Dysfunctional autism risk genes cause circuit-specific connectivity deficits with distinct developmental trajectories. Cereb. Cortex 28, 2495–2506 (2018). (PMID: 29901787599896110.1093/cercor/bhy046)
Perge, J. A., Niven, J. E., Mugnaini, E., Balasubramanian, V. & Sterling, P. Why do axons differ in caliber? J. Neurosci. 32, 626–638 (2012). (PMID: 22238098357169710.1523/JNEUROSCI.4254-11.2012)
Shen, M. et al. Reduced mitochondrial fusion and Huntingtin levels contribute to impaired dendritic maturation and behavioral deficits in Fmr1-mutant mice. Nat. Neurosci. 22, 386–400 (2019). (PMID: 30742117655689210.1038/s41593-019-0338-y)
Akins, M. R. et al. Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains. Hum. Mol. Genet. 26, 192–209 (2017). (PMID: 28082376)
معلومات مُعتمدة: F31 MH115656 United States MH NIMH NIH HHS
المشرفين على المادة: 0 (Fmr1 protein, rat)
139135-51-6 (Fragile X Mental Retardation Protein)
تواريخ الأحداث: Date Created: 20200814 Date Completed: 20210618 Latest Revision: 20220531
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7423986
DOI: 10.1038/s41398-020-00943-x
PMID: 32788572
قاعدة البيانات: MEDLINE
الوصف
تدمد:2158-3188
DOI:10.1038/s41398-020-00943-x