Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/64302

TítuloMonoamine deficits in the brain of methyl-CpG binding protein 2 null mice suggest the involvement of the cerebral cortex in early stages of Rett syndrome
Autor(es)Santos, M.
Summavielle, T.
Teixeira-Castro, A.
Silva-Fernandes, Anabela
Duarte-Silva, S.
Marques, Fernanda
Martins, L.
Dierssen, M.
Oliveira, P.
Sousa, Nuno
Maciel, P.
Palavras-chaveAge Factors
Animals
Ataxia
Behavior, Animal
Brain
DNA-Binding Proteins
Disease Models, Animal
Gene Expression Regulation
Male
Mice
Mice, Knockout
Monoamine Oxidase
Motor Activity
Nitric Oxide Synthase Type I
Norepinephrine
Rett Syndrome
Serotonin
Tryptophan Hydroxylase
Tyrosine 3-Monooxygenase
Vesicle-Associated Membrane Protein 2
RTT
Neurodevelopment
Autism
Mental retardation
Data13-Out-2010
EditoraElsevier
RevistaNeuroscience
CitaçãoSantos, M., Summavielle, T., Teixeira-Castro, A., Silva-Fernandes, A., et. al. (2010). Monoamine deficits in the brain of methyl-CpG binding protein 2 null mice suggest the involvement of the cerebral cortex in early stages of Rett syndrome. Neuroscience, 170(2), 453-467
Resumo(s)Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 gene (MECP2). Several neural systems are affected in Rett, resulting in an autonomic dysfunction, a movement disorder with characteristic loss of locomotor abilities and profound cognitive impairments. A deregulation of monoamines has been detected in the brain and cerebrospinal fluid of both Rett patients and a Rett syndrome murine model, the Mecp2 knock-out mouse. Our goal was to characterize the onset and progression of motor dysfunction in Mecp2(tm1.1Bird) knock-out mice and the possible neurochemical alterations in different brain regions potentially playing a role in Rett-like pathophysiology, at two different time-points, at weaning (3 weeks old) and in young adults when overt symptoms are observed (8 weeks old). Our results revealed significant age- and region-dependent impairments in these modulatory neurotransmitter systems that correspond well with the motor phenotype observed in these mice. At 3 weeks of age, male Mecp2 knock-out mice exhibited ataxia and delayed motor initiation. At this stage, noradrenergic and serotonergic transmission was mainly altered in the prefrontal and motor cortices, whereas during disease progression the neurochemical changes were also observed in hippocampus and cerebellum. Our data suggest that the deregulation of norepinephrine and serotonin systems in brain regions that participate in motor control are involved in the pathophysiology of Rett syndrome motor phenotypes. Moreover, we highlight the contribution of cortical regions along with the brainstem to be in the origin of the pathology and the role of hippocampus and cerebellum in the progression of the disease rather than in its establishment.
TipoArtigo
URIhttps://hdl.handle.net/1822/64302
DOI10.1016/j.neuroscience.2010.07.010
ISSN0306-4522
e-ISSN1873-7544
Versão da editorahttps://www.sciencedirect.com/science/article/pii/S0306452210009887
Arbitragem científicayes
AcessoAcesso restrito UMinho
Aparece nas coleções:ICVS - Artigos em revistas internacionais / Papers in international journals

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