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Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons.
Wu, Lien-Szu; Cheng, Wei-Cheng; Chen, Chia-Ying; Wu, Ming-Che; Wang, Yi-Chi; Tseng, Yu-Hsiang; Chuang, Trees-Juen; Shen, C-K James.
Afiliação
  • Wu LS; Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 115, Taiwan, Republic of China.
  • Cheng WC; Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 115, Taiwan, Republic of China.
  • Chen CY; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Wu MC; Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 115, Taiwan, Republic of China.
  • Wang YC; Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan, Republic of China.
  • Tseng YH; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Chuang TJ; Genomics Research Center, Academia Sinica, Taipei, Taiwan. trees@gate.sinica.edu.tw.
  • Shen CJ; Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 115, Taiwan, Republic of China. ckshen@gate.sinica.edu.tw.
Acta Neuropathol Commun ; 7(1): 50, 2019 03 29.
Article em En | MEDLINE | ID: mdl-30922385
TAR DNA-binding protein (TDP-43) is a ubiquitously expressed nuclear protein, which participates in a number of cellular processes and has been identified as the major pathological factor in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we constructed a conditional TDP-43 mouse with depletion of TDP-43 in the mouse forebrain and find that the mice exhibit a whole spectrum of age-dependent frontotemporal dementia-like behaviour abnormalities including perturbation of social behaviour, development of dementia-like behaviour, changes of activities of daily living, and memory loss at a later stage of life. These variations are accompanied with inflammation, neurodegeneration, and abnormal synaptic plasticity of the mouse CA1 neurons. Importantly, analysis of the cortical RNA transcripts of the conditional knockout mice at the pre-/post-symptomatic stages and the corresponding wild type mice reveals age-dependent alterations in the expression levels and RNA processing patterns of a set of genes closely associated with inflammation, social behaviour, synaptic plasticity, and neuron survival. This study not only supports the scenario that loss-of-function of TDP-43 in mice may recapitulate key behaviour features of the FTLD diseases, but also provides a list of TDP-43 target genes/transcript isoforms useful for future therapeutic research.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Prosencéfalo / Proteínas de Ligação a DNA / Demência Frontotemporal / Transcriptoma / Neurônios Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Prosencéfalo / Proteínas de Ligação a DNA / Demência Frontotemporal / Transcriptoma / Neurônios Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article