FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2911295890> ?p ?o ?g. }

• W2911295890 endingPage "4828" @default.
• W2911295890 startingPage "4814" @default.
• W2911295890 abstract "Pathogenic mutations in cyclin-dependent kinase-like 5 (<i>CDKL5</i>) result in CDKL5 deficiency disorder (CDD), a rare disease marked by early-life seizures, autistic behaviors, and intellectual disability. Although mouse models of CDD exhibit dendritic instability and alterations in synaptic scaffolding proteins, studies of glutamate receptor levels and function are limited. Here we used a novel mouse model of CDD, the <i>Cdkl5^R59X</i> knock-in mouse (R59X), to investigate changes in synaptic glutamate receptor subunits and functional consequences. Male mice were used for all experiments to avoid the confounding effects of X-inactivation that would be present in female heterozygous mice. We showed that adult male R59X mice recapitulated the behavioral outcomes observed in other mouse models of CDD, including social deficits and memory and learning impairments, and exhibited decreased latency to seizure upon pentylenetetrazol administration. Furthermore, we observed a specific increase in GluA2-lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors (AMPARs) in the adult R59X hippocampus, which is accompanied electrophysiologically by increased rectification ratio of AMPAR EPSCs and elevated early-phase long term potentiation (LTP). Finally, we showed that acute treatment with the GluA2-lacking AMPAR blocker IEM-1460 decreased AMPAR currents, and rescued social deficits, working memory impairments, and seizure behavior latency in R59X mice. <b>SIGNIFICANCE STATEMENT</b> CDKL5 deficiency disorder (CDD) is a rare disease marked by autistic-like behaviors, intellectual disability, and seizures. While synaptic dysfunction has been observed in mouse models of CDD, there is limited information on how synaptic alterations contribute to behavioral and functional changes in CDD. Here we reveal elevated hippocampal GluA2-lacking AMPAR expression in a novel mouse model of CDD that is accompanied by changes in synaptic AMPAR function and plasticity. We also show, for the first time, that acutely targeting GluA2-lacking AMPAR dysregulation rescues core synaptic and neurobehavioral deficits in CDD." @default.
• W2911295890 created "2019-02-21" @default.
• W2911295890 creator A5059417834 @default.
• W2911295890 creator A5061965040 @default.
• W2911295890 creator A5085753558 @default.
• W2911295890 date "2019-04-05" @default.
• W2911295890 modified "2023-10-13" @default.
• W2911295890 title "AMPA Receptor Dysregulation and Therapeutic Interventions in a Mouse Model of CDKL5 Deficiency Disorder" @default.
• W2911295890 cites W1254699444 @default.
• W2911295890 cites W1548600249 @default.
• W2911295890 cites W1559742681 @default.
• W2911295890 cites W1967209558 @default.
• W2911295890 cites W1970629813 @default.
• W2911295890 cites W1979266787 @default.
• W2911295890 cites W1984458059 @default.
• W2911295890 cites W1985351207 @default.
• W2911295890 cites W1988625486 @default.
• W2911295890 cites W1988945207 @default.
• W2911295890 cites W1989938166 @default.
• W2911295890 cites W1991251463 @default.
• W2911295890 cites W1991816820 @default.
• W2911295890 cites W1992783328 @default.
• W2911295890 cites W1992946532 @default.
• W2911295890 cites W1993536619 @default.
• W2911295890 cites W1993782794 @default.
• W2911295890 cites W1997862361 @default.
• W2911295890 cites W1999024554 @default.
• W2911295890 cites W2001456267 @default.
• W2911295890 cites W2014696835 @default.
• W2911295890 cites W2019179420 @default.
• W2911295890 cites W2020931572 @default.
• W2911295890 cites W2022050193 @default.
• W2911295890 cites W2022857328 @default.
• W2911295890 cites W2026832087 @default.
• W2911295890 cites W2033179944 @default.
• W2911295890 cites W2036316060 @default.
• W2911295890 cites W2037479294 @default.
• W2911295890 cites W2041249574 @default.
• W2911295890 cites W2049021349 @default.
• W2911295890 cites W2049868560 @default.
• W2911295890 cites W2050322614 @default.
• W2911295890 cites W2050597016 @default.
• W2911295890 cites W2052477543 @default.
• W2911295890 cites W2057250808 @default.
• W2911295890 cites W2058571616 @default.
• W2911295890 cites W2060855064 @default.
• W2911295890 cites W2063439606 @default.
• W2911295890 cites W2065579814 @default.
• W2911295890 cites W2072281697 @default.
• W2911295890 cites W2074385487 @default.
• W2911295890 cites W2076018693 @default.
• W2911295890 cites W2076566560 @default.
• W2911295890 cites W2078936052 @default.
• W2911295890 cites W2083974405 @default.
• W2911295890 cites W2084522972 @default.
• W2911295890 cites W2089663252 @default.
• W2911295890 cites W2093151201 @default.
• W2911295890 cites W2093910259 @default.
• W2911295890 cites W2100064902 @default.
• W2911295890 cites W2101752858 @default.
• W2911295890 cites W2106645298 @default.
• W2911295890 cites W2110534885 @default.
• W2911295890 cites W2111977586 @default.
• W2911295890 cites W2124363259 @default.
• W2911295890 cites W2125677514 @default.
• W2911295890 cites W2127241254 @default.
• W2911295890 cites W2127311839 @default.
• W2911295890 cites W2138499080 @default.
• W2911295890 cites W2143497500 @default.
• W2911295890 cites W2147140183 @default.
• W2911295890 cites W2147561535 @default.
• W2911295890 cites W2149119305 @default.
• W2911295890 cites W2208766333 @default.
• W2911295890 cites W2281938202 @default.
• W2911295890 cites W2292245145 @default.
• W2911295890 cites W2298009876 @default.
• W2911295890 cites W2320983896 @default.
• W2911295890 cites W2335818909 @default.
• W2911295890 cites W2509522099 @default.
• W2911295890 cites W2513828441 @default.
• W2911295890 cites W2567675045 @default.
• W2911295890 cites W2581719304 @default.
• W2911295890 cites W2642984943 @default.
• W2911295890 cites W2733418771 @default.
• W2911295890 cites W2734147076 @default.
• W2911295890 cites W2768133112 @default.
• W2911295890 cites W2770631390 @default.
• W2911295890 cites W2774694784 @default.
• W2911295890 cites W2783311163 @default.
• W2911295890 cites W2789974830 @default.
• W2911295890 cites W2794784712 @default.
• W2911295890 cites W2802180211 @default.
• W2911295890 cites W2886834730 @default.
• W2911295890 cites W2895740282 @default.
• W2911295890 cites W2899728099 @default.
• W2911295890 doi "https://doi.org/10.1523/jneurosci.2041-18.2019" @default.
• W2911295890 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6561688" @default.
• W2911295890 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30952813" @default.

• next