期刊
NEUROBIOLOGY OF AGING
卷 36, 期 4, 页码 1702-1715出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.01.004
关键词
F3/contactin; Aging; Long-term potentiation; Memory; Amyloid-precursor protein cleavage; Amyloid-beta; Apoptosis; Brain-derived neurotrophic factor; cAMP-responsive element binding
资金
- Neuroscience Program-Compagnia di San Paolo [2008.2363]
- Italian Ministry of University, Research Program of Relevant National Interest
- Regione Puglia (PON D.A.Re. Project)
- Bari University
- Fondazione Cassa di Risparmio di Puglia
- European Union (PON Infrastructures)
We have recently shown that overexpression of the F3/contactin adhesive glycoprotein (also known as Contactin-1) promotes neurogenesis in adult hippocampus, which correlates with improved synaptic plasticity and memory. Because F3/contactin levels physiologically decrease with age, here, we aim at investigating whether its overexpression might counteract the cognitive decline in aged animals. For this we use 20- to 24-month-old TAG/F3 transgenic mice in which F3/contactin overexpression is driven by regulatory sequences from the gene encoding the transient axonal glycoprotein TAG-1 throughout development. We show that aged TAG/F3 mice display improved hippocampal long-term potentiation and memory compared with wild-type littermates. The same mice undergo a decrease of neuronal apoptosis at the hippocampal level, which correlated to a decrease of active caspase-3; by contrast, procaspase-3 and Bax as well as the anti-apoptotic and plasticity-related pathway BDNF/CREB/Bcl-2 were rather increased. Interestingly, amyloid-precursor protein processing was shifted toward sAPP alpha generation, with a decrease of sAPP beta and amyloid-beta levels. Our data confirm that F3/contactin plays a role in hippocampal synaptic plasticity and memory also in aged mice, suggesting that it acts on molecular pathways related to apoptosis and amyloid-beta production. (C) 2015 Elsevier Inc. All rights reserved.
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