Simultaneous Alteration of the Circadian Variation of Memory, Hippocampal Synaptic Plasticity, and Metabolism in a Triple Transgenic Mouse Model of Alzheimer's Disease

• Autor(a) principal: Carvalho da Silva, António M
• Data de Publicação: 2022
• Outros Autores: Lemos, Cristina, Silva, Henrique Bernardo, Ferreira, Ildete L., Tomé, Ângelo R., Rego, A. Cristina, Cunha, Rodrigo A.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• DOI: 10.3389/fnagi.2022.835885
• Texto Completo: http://hdl.handle.net/10316/103249; https://doi.org/10.3389/fnagi.2022.835885
• topic: circadian; Alzheimer’s disease; behavior; LTP; mitochondria; Zeitgeber; hippocampus

Alzheimer's disease (AD) is characterized by progressive memory deficits accompanied by synaptic and metabolic deficits, namely of mitochondrial function. AD patients also display a disrupted circadian pattern. Thus, we now compared memory performance, synaptic plasticity, and mitochondria function in 24-week-old non-transgenic (non-Tg) and triple transgenic male mice modeling AD (3xTg-AD) at Zeitgeber 04 (ZT-4, inactive phase) and ZT-16 (active phase). Using the Morris water maze test to minimize the influence of circadian-associated locomotor activity, we observed a circadian variation in hippocampus-dependent learning performance in non-Tg mice, which was impaired in 3xTg-AD mice. 3xTg-AD mice also displayed a lack of circadian variation of their performance in the reversal spatial learning task. Additionally, the amplitude of hippocampal long-term potentiation also exhibited a circadian profile in non-Tg mice, which was not observed in 3xTg-AD mice. Moreover, cerebral cortical synaptosomes of non-Tg mice also displayed a circadian variation of FCCP-stimulated oxygen consumption as well as in mitochondrial calcium retention that were blunted in 3xTg-AD mice. In sum, this multidimensional study shows that the ability to maintain a circadian oscillation in brain behavior, synaptic plasticity, and synaptic mitochondria function are simultaneously impaired in 3xTg-AD mice, highlighting the effects of circadian misalignment in AD.