We have previously shown that overexpression of the F3/contactin cell-adhesion molecule in the hippocampus promotes adult neurogenesis and improves synaptic plasticity and memory. Because F3/contactin levels physiologically decrease with age, here we aimed to investigate whether its overexpression might counteract the cognitive decline in aged mice. We used 20-24 month-old wild type and transgenic (Tg) mice in which F3/contactin expression is driven by TAG-1 gene regulatory sequences (TAG/F3 mice), undergoing an increased expression of F3/contactin in the forebrain in late development. We performed electrophysiological and behavioral studies to explore hippocampal synaptic plasticity (long-term potentiation, LTP, at CA1 area) and memory (spatial learning, reference memory and recognition memory). We also evaluated the expression of Caspase-3, Bax, Bcl-2, BDNF and CREB and we analyzed amyloid precursor protein (APP) processing toward amyloid-beta (Abeta) production. We found that aged TAG/F3 homozygous mice presented an improvement of LTP and memory compared to aged wild type littermates. Moreover, the increased expression of pro-apoptotic molecules (Caspase-3 and Bax) in old Tg animals was counteracted by a concomitant activation of the anti-apoptotic and plasticity-related pathway BDNF/CREB/Bcl-2. Interestingly, APP processing was shifted toward sAPPalpha generation, with a consequent decrease of sAPPbeta, Abeta42 levels and Abeta42/40 ratio. Our data suggest that F3/contactin plays a role in hippocampal synaptic plasticity and memory in old mice, probably by acting on molecular pathways related to apoptosis and Abeta production. These findings might be relevant for new therapeutical approaches against the impairment of learning and memory during aging.
|Titolo:||F3/contactin overexpression rescues synaptic plasticity and memory in aged mice|
|Data di pubblicazione:||2014|
|Citazione:||F3/contactin overexpression rescues synaptic plasticity and memory in aged mice / Puzzo D; Bizzoca A; Guida CA; Gulisano W; Frasca G; Bellomo M; Gennarini G. - (2014). ((Intervento presentato al convegno Society for Neuroscience 2014 tenutosi a WASHINGTON DC, USA. nel Nov 15-19, 2014.|
|Appare nelle tipologie:||4.1 Contributo in Atti di convegno|