Navegando por Palavras-chave "Neurodegenerative disorders"

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    Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission
    (Associação Brasileira de Divulgação Científica, 2013-01-01) Queiroz, Claudio Marcos [UNIFESP]; Tiba, Paula Ayko; Moreira, Karin Monteiro [UNIFESP]; Guidine, Patrícia Alves Maia; Rezende, Gustavo H S; Moraes, Márcio Flávio Dutra; Prado, Marco Antônio Máximo; Prado, Vânia Ferreira; Tufik, Sergio [UNIFESP]; Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Rio Grande do Norte Instituto do Cerebro; Universidade Federal do ABC Computacao e Cognicao Centro de Matematica; Universidade Federal de Minas Gerais Departamento de Fisiologia e Biofisica Nucleo de Neurociencias; University of Western Ontario Department of Physiology and Pharmacology and Department of Anatomy and Cell Biology Robarts Research Institute
    Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.