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Title: | Simultaneous Alteration of the Circadian Variation of Memory, Hippocampal Synaptic Plasticity, and Metabolism in a Triple Transgenic Mouse Model of Alzheimer's Disease | Authors: | Carvalho da Silva, António M Lemos, Cristina Silva, Henrique Bernardo Ferreira, Ildete L. Tomé, Ângelo R. Rego, A. Cristina Cunha, Rodrigo A. |
Keywords: | circadian; Alzheimer’s disease; behavior; LTP; mitochondria; Zeitgeber; hippocampus | Issue Date: | 2022 | Project: | La Caixa Foundation (LCF/PR/HP17/52190001) Centro 2020 (CENTRO-01- 0145-FEDER-000008:BrainHealth 2020, CENTRO-01-0145- FEDER-000012-HealthyAging2020, and CENTRO-01-0246- FEDER-000010) FCT - POCI-01-0145-FEDER-03127, POCI-01-0145-FEDER-032316, UIDP/04539/2020, and UIDB/04539/2020) FCT - SFRH/BD/51667/2011 |
Serial title, monograph or event: | Frontiers in Aging Neuroscience | Volume: | 14 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/103249 | ISSN: | 1663-4365 | DOI: | 10.3389/fnagi.2022.835885 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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