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Functional aspects of early brain development are preserved in tuberous sclerosis complex (TSC) epileptogenic lesions

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10327793" target="_blank" >RIV/00064203:_____/16:10327793 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11130/16:10327793

  • Result on the web

    <a href="http://dx.doi.org/10.1016/j.nbd.2016.07.014" target="_blank" >http://dx.doi.org/10.1016/j.nbd.2016.07.014</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.nbd.2016.07.014" target="_blank" >10.1016/j.nbd.2016.07.014</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Functional aspects of early brain development are preserved in tuberous sclerosis complex (TSC) epileptogenic lesions

  • Original language description

    Tuberous sclerosis complex (TSC) is a rare multi-system genetic disease characterized by several neurological disorders, the most common of which is the refractory epilepsy caused by highly epileptogenic cortical lesions. Previous studies suggest an alteration of GABAergic and glutamatergic transmission in TSC brain indicating an unbalance of excitation/inhibition that can explain, at least in part, the high incidence of epilepsy in these patients. Here we investigate whether TSC cortical tissues could retain GABA(A) and AMPA receptors at early stages of human brain development thus contributing to the generation and recurrence of seizures. Given the limited availability of pediatric human brain specimens, we used the microtransplantation method of injecting Xenopus oocytes with membranes from TSC cortical tubers and control brain tissues. Moreover, qPCR was performed to investigate the expression of GABA(A) and AMPA receptor subunits (GABA(A) alpha 1-5, beta 3, gamma 2, delta, GluA2) and cation chloride co-transporters NKCC1 and KCC2. The evaluation of nine human cortical brain samples, from 15 gestation weeks to 15 years old, showed a progressive shift towards more hyperpolarized GABAA reversal potential (E-GABA). This shift was associated with a differential expression of the chloride cotransporters NKCC1 and KCC2. Furthermore, the GluA1/GIuA2 mRNA ratio of expression paralleled the development process. On the contrary, in oocytes micro-transplanted with epileptic TSC tuber tissue from seven patients, neither the GABA(A) reversal potential nor the GluA1/GIuA2 expression showed similar developmental changes. Our data indicate for the first time, that in the same cohort of TSC patients, the pattern of both GABA(A)R and G1uA1/G1uA2 functions retains features that are typical of an immature brain. These observations support the potential contribution of altered receptor function to the epileptic disorder of TSC and may suggest novel therapeutic approaches.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    FH - Neurology, neuro-surgery, nuero-sciences

  • OECD FORD branch

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Neurobiology of Disease

  • ISSN

    0969-9961

  • e-ISSN

  • Volume of the periodical

    95

  • Issue of the periodical within the volume

    November

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    9

  • Pages from-to

    93-101

  • UT code for WoS article

    000383412200009

  • EID of the result in the Scopus database

    2-s2.0-84978733864