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• W3217645793 abstract "Hyperactivation of the mTOR pathway during foetal neurodevelopment alters neuron structure and function, leading to focal malformation of cortical development and intractable epilepsy. Recent evidence suggests a role for dysregulated cap-dependent translation downstream of mTOR signalling in the formation of focal malformation of cortical development and seizures. However, it is unknown whether modifying translation once the developmental pathologies are established can reverse neuronal abnormalities and seizures. Addressing these issues is crucial with regards to therapeutics because these neurodevelopmental disorders are predominantly diagnosed during childhood, when patients present with symptoms. Here, we report increased phosphorylation of the mTOR effector and translational repressor, 4E-BP1, in patient focal malformation of cortical development tissue and in a mouse model of focal malformation of cortical development. Using temporally regulated conditional gene expression systems, we found that expression of a constitutively active form of 4E-BP1 that resists phosphorylation by focal malformation of cortical development in juvenile mice reduced neuronal cytomegaly and corrected several neuronal electrophysiological alterations, including depolarized resting membrane potential, irregular firing pattern and aberrant expression of HCN4 ion channels. Further, 4E-BP1 expression in juvenile focal malformation of cortical development mice after epilepsy onset resulted in improved cortical spectral activity and decreased spontaneous seizure frequency in adults. Overall, our study uncovered a remarkable plasticity of the juvenile brain that facilitates novel therapeutic opportunities to treat focal malformation of cortical development-related epilepsy during childhood with potentially long-lasting effects in adults." @default.
• W3217645793 created "2021-12-06" @default.
• W3217645793 creator A5012414516 @default.
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• W3217645793 date "2021-11-25" @default.
• W3217645793 modified "2023-10-12" @default.
• W3217645793 title "Expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy" @default.
• W3217645793 cites W1580041071 @default.
• W3217645793 cites W1905762853 @default.
• W3217645793 cites W1978116811 @default.
• W3217645793 cites W1979458957 @default.
• W3217645793 cites W1980261528 @default.
• W3217645793 cites W1980480824 @default.
• W3217645793 cites W1987555879 @default.
• W3217645793 cites W1992480202 @default.
• W3217645793 cites W2000825257 @default.
• W3217645793 cites W2002226709 @default.
• W3217645793 cites W2003082472 @default.
• W3217645793 cites W2020054918 @default.
• W3217645793 cites W2027426666 @default.
• W3217645793 cites W2035149992 @default.
• W3217645793 cites W2038616814 @default.
• W3217645793 cites W2039918425 @default.
• W3217645793 cites W2049671028 @default.
• W3217645793 cites W2053955820 @default.
• W3217645793 cites W2054498084 @default.
• W3217645793 cites W2055834662 @default.
• W3217645793 cites W2061066931 @default.
• W3217645793 cites W2064656431 @default.
• W3217645793 cites W2068139469 @default.
• W3217645793 cites W2070555834 @default.
• W3217645793 cites W2075026706 @default.
• W3217645793 cites W2075055741 @default.
• W3217645793 cites W2075511135 @default.
• W3217645793 cites W2076174029 @default.
• W3217645793 cites W2097625706 @default.
• W3217645793 cites W2097794137 @default.
• W3217645793 cites W2100046131 @default.
• W3217645793 cites W2105727230 @default.
• W3217645793 cites W2106822551 @default.
• W3217645793 cites W2107449228 @default.
• W3217645793 cites W2111444310 @default.
• W3217645793 cites W2115476694 @default.
• W3217645793 cites W2116809499 @default.
• W3217645793 cites W2128367294 @default.
• W3217645793 cites W2133947591 @default.
• W3217645793 cites W2139856846 @default.
• W3217645793 cites W2145360633 @default.
• W3217645793 cites W2153295642 @default.
• W3217645793 cites W2154024784 @default.
• W3217645793 cites W2156941752 @default.
• W3217645793 cites W2160106765 @default.
• W3217645793 cites W2162919051 @default.
• W3217645793 cites W2214989086 @default.
• W3217645793 cites W2218878453 @default.
• W3217645793 cites W2296707446 @default.
• W3217645793 cites W2314705006 @default.
• W3217645793 cites W2316099676 @default.
• W3217645793 cites W2338771128 @default.
• W3217645793 cites W2413290533 @default.
• W3217645793 cites W2474276490 @default.
• W3217645793 cites W2522175331 @default.
• W3217645793 cites W2593816418 @default.
• W3217645793 cites W2605388121 @default.
• W3217645793 cites W2613494796 @default.
• W3217645793 cites W2615129326 @default.
• W3217645793 cites W2617940752 @default.
• W3217645793 cites W2793783592 @default.
• W3217645793 cites W2795386622 @default.
• W3217645793 cites W2802211669 @default.
• W3217645793 cites W2884747888 @default.
• W3217645793 cites W2886019038 @default.
• W3217645793 cites W2886828822 @default.
• W3217645793 cites W2888204354 @default.
• W3217645793 cites W2896869836 @default.
• W3217645793 cites W2902187913 @default.
• W3217645793 cites W2913672248 @default.
• W3217645793 cites W2914727006 @default.
• W3217645793 cites W2922759833 @default.
• W3217645793 cites W2945737519 @default.
• W3217645793 cites W2953787680 @default.
• W3217645793 cites W2966400261 @default.
• W3217645793 cites W2967766849 @default.
• W3217645793 cites W2972471297 @default.
• W3217645793 cites W2979535796 @default.
• W3217645793 cites W3007821824 @default.
• W3217645793 cites W3025124464 @default.
• W3217645793 cites W3041533218 @default.
• W3217645793 cites W3082207824 @default.
• W3217645793 cites W3083080967 @default.
• W3217645793 cites W3085824629 @default.
• W3217645793 cites W3086930903 @default.

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