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2020

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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ABNORMAL EXPRESSION OF CEREBROSPINAL FLUID CATION CHLORIDE COTRANSPORTERS IN PATIENTS WITH RETT SYNDROME.

Sofia Temudo Duarte (1,4,5), Judith Armstrong (1,3), Ana Roche (1), Carlos Ortez (1,3), Ana Perez (1), Maria del Mar O’Callaghan (1), Antonina Pereira(4), FrancescSanmartı ́(1), Aida Ormazabal (2,3), Rafael Artuch (2,3), Mercedes Pineda (1,3), Angels Garcia-Cazorla (1,3)

1 Department of Neurology, Hospital Sant Joan de Deu (HSJD), Barcelona, Spain, 2 Department of Biochemistry, Hospital Sant Joan de Deu (HSJD), Barcelona, Spain,; 3 CIBER-ER (Biomedical Network Research Centre onRareDiseases, Instituto de Salud Carlos III), Madrid, Spain; 4 Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; 51Serviço de Neurología Pediátrica, Hospital D. Estefânia, CHLC,Lisboa, Portugal.

PLoS One. 2013 Jul 19;8(7):e68851. doi: 10.1371/journal.pone.0068851 (artigo)

Objective
Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs) play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group.

Methods
The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life) and from Rett syndrome patients (2 to 19 years of life), by immunoblot analysis.

Results
Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group.

Conclusions
Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.

Keywords: Rett Syndrome, cerebrospinal fluid, cation chloride cotransporters