Capsosiphon fulvescens glycopeptides restore synaptic plasticity and mitigate cognitive decline via calcineurin...

Age-related cognitive decline and synaptic loss are associated with alterations in hippocampal synaptic protein phosphorylation and signaling pathways. Natural compounds from marine sources, such as Capsosiphon fulvescens glycopeptides (Cf-tPep), have shown potential neuroprotective properties. This study aimed to investigate the effects of trypsinized glycopeptides from C. fulvescens on synaptic protein phosphorylation and cognitive function in aging hippocampal neurons and rats.

The research employed both in vitro and in vivo experimental models to evaluate the impact of Cf-tPep on aged hippocampal neurons and cognitive function in rats. Primary hippocampal neurons from rats were cultured for 49 days to model aging. Synaptic protein expression and phosphorylation were analyzed through Western blotting, immunoprecipitation, and double-immunofluorescence. In vivo, aged rats received Cf-tPep via hippocampal microinjection using osmotic pumps. Cognitive function was assessed using the Morris water maze test.

Cf-tPep treatment restored phosphorylation levels of synaptic proteins, including PSD95 (S295) and GluN2B (Y1472), in aged neurons. This effect was mediated through inhibition of the calcineurin-STEP signaling pathway and activation of CaMKII-ERK1/2 signaling, enhancing synaptic plasticity and reducing neuronal senescence. In aged rats, Cf-tPep improved spatial learning and memory retention by modulating synaptic protein phosphorylation.

Trypsinized glycopeptides from C. fulvescens show promise as a therapeutic agent for alleviating age-related cognitive decline through regulation of synaptic signaling pathways. These findings suggest their potential for promoting brain health in the elderly.