Age-Related Cognitive and Motor Decline in a Mouse Model of CDKL5 Deficiency Disorder is Associated with Increased Neuronal Senescence and Death.

Aging and Disease
Laura GennaccaroCiani Elisabetta

Abstract

CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. Children affected by CDD display a clinical phenotype characterized by early-onset epilepsy, intellectual disability, motor impairment, and autistic-like features. Although the clinical aspects associated with CDKL5 mutations are well described in children, adults with CDD are still under-characterized. Similarly, most animal research has been carried out on young adult Cdkl5 knockout (KO) mice only. Since age represents a risk factor for the worsening of symptoms in many neurodevelopmental disorders, understanding age differences in the development of behavioral deficits is crucial in order to optimize the impact of therapeutic interventions. Here, we compared young adult Cdkl5 KO mice with middle-aged Cdkl5 KO mice, at a behavioral, neuroanatomical, and molecular level. We found an age-dependent decline in motor, cognitive, and social behaviors in Cdkl5 KO mice, as well as in breathing and sleep patterns. The behavioral decline in older Cdkl5 KO mice was not associated with a worsening of neuroanatomical alterations, such as decreased dendritic arborization or spine density, but was paralleled by decreased ne...Continue Reading

References

Jan 27, 2000·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·X ZhenE Friedman
Jun 11, 2004·Nature·Tao LuBruce A Yankner
Oct 30, 2007·Neuron·Eric CourchesneJohn Morgan
Nov 9, 2007·Neuron·Maria Chahrour, Huda Y Zoghbi
Sep 16, 2008·Brain : a Journal of Neurology·Nadia Bahi-BuissonThierry Bienvenu
Jun 30, 2010·Journal of Neurodevelopmental Disorders·Agustini UtariRandi J Hagerman
Jul 19, 2011·Journal of Child Neurology·Xenia L StalpersAad Verrips
Aug 9, 2012·European Journal of Human Genetics : EJHG·Stephanie FehrJohn Christodoulou
Dec 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·I-Ting Judy WangZhaolan Zhou
Feb 9, 2013·Sleep Medicine Reviews·Laura PalaginiDieter Riemann
May 4, 2013·Journal of Neurodevelopmental Disorders·Jason J WolffJoseph Piven
Apr 20, 2014·Neuron·Daniel MeyerVolker Scheuss
May 20, 2014·PloS One·Elena AmendolaCornelius T Gross
Jul 6, 2015·Neurobiology of Disease·Claudia FuchsElisabetta Ciani
Oct 11, 2015·Biological Psychiatry·Grazia Della SalaTommaso Pizzorusso
Nov 26, 2015·Life Sciences·Sulagna Dutta, Pallav Sengupta
Dec 25, 2015·American Journal on Intellectual and Developmental Disabilities·Anna J EsbensenRyan Macks
Apr 16, 2016·Orphanet Journal of Rare Diseases·Meghana MangattJenny Downs
Jul 29, 2016·Human Molecular Genetics·Stefania TrazziElisabetta Ciani
Feb 24, 2017·Journal of Sleep Research·Viviana Lo MartireGiovanna Zoccoli
Mar 17, 2017·Autism Research : Official Journal of the International Society for Autism Research·Manon GauducheauSusanna Pietropaolo
Apr 4, 2017·Human Molecular Genetics·Raffaele MazziottiTommaso Pizzorusso
Jul 5, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sheng TangZhaolan Zhou
Feb 20, 2018·The Journal of Clinical Investigation·Darren J Baker, Ronald C Petersen
Feb 24, 2018·Human Molecular Genetics·Stefania TrazziElisabetta Ciani
Apr 5, 2018·Human Molecular Genetics·Marco TramarinCharlotte Kilstrup-Nielsen
Mar 29, 2019·Journal of Sleep Research·Stefano BastianiniGiovanna Zoccoli
Apr 7, 2019·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Madhumita YennawarFrances E Jensen
May 21, 2019·Human Molecular Genetics·Leonardo LuporiTommaso Pizzorusso
May 31, 2019·Pediatric Neurology·Scott DemarestTim A Benke
Jun 6, 2019·Aging and Disease·Kunyu LiSong Qin
Feb 1, 2020·Molecular Neurobiology·Manuela LoiElisabetta Ciani

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Citations

Jul 10, 2021·Journal of Neuroinflammation·Giuseppe GalvaniStefania Trazzi

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Software Mentioned

Matlab Psychtoolbox
EthoVision
GraphPad Prism
SPSS
ImageJ
Image Pro Plus
Immagini
Image LabTM

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