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Title: Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease
Authors: Lopes, Cátia R. 
Silva, Joana S
Santos, Joana 
Rodrigues, Matilde S. 
Madeira, Daniela 
Oliveira, Andreia 
Moreira-de-Sá, Ana 
Lourenço, Vanessa S. 
Gonçalves, Francisco Q. 
Silva, Henrique B. 
Simões, Ana Patrícia
Rolo, Anabela P. 
Canas, Paula M. 
Tomé, Ângelo R. 
Palmeira, Carlos M. 
Lopes, João Pedro 
Cunha, Rodrigo A. 
Agostinho, Paula M. 
Ferreira, Samira G. 
Keywords: Alzheimer’s disease; APP/PS1 mice; memory; LTP; sirtuins; prefrontal cortex; synapse
Issue Date: 9-Apr-2023
Publisher: MDPI
Project: LCF/PR/HP17/52190001 
CENTRO- 01-0145-FEDER-000008 
POCI-01- 0145-FEDER-03127 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 24
Issue: 8
Abstract: Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.
ISSN: 1422-0067
DOI: 10.3390/ijms24086968
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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