| Autor: |
Cátia R. Lopes, Joana S. Silva, Joana Santos, Matilde S. Rodrigues, Daniela Madeira, Andreia Oliveira, Ana Moreira-de-Sá, Vanessa S. Lourenço, Francisco Q. Gonçalves, Henrique B. Silva, Ana Patrícia Simões, Anabela P. Rolo, Paula M. Canas, Ângelo R. Tomé, Carlos M. Palmeira, João Pedro Lopes, Rodrigo A. Cunha, Paula Agostinho, Samira G. Ferreira |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences; Volume 24; Issue 8; Pages: 6968 |
| ISSN: |
1422-0067 |
| DOI: |
10.3390/ijms24086968 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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