SummaryThe structural and functional plasticity of synapses is critical for learning and memory. Long-term potentiation (LTP) induction promotes spine growth and AMPAR accumulation at excitatory synapses, leading to increased synaptic strength. Glutamate initiates these processes, but the contribution from extracellular modulators is not fully established. Wnts are required for spine formation; however, their impact on activity-mediated spine plasticity and AMPAR localization is unknown. We found that LTP induction rapidly increased synaptic Wnt7a/b protein levels. Acute blockade of endogenous Wnts or loss of postsynaptic Frizzled-7 (Fz7) receptors impaired LTP-mediated synaptic strength, spine growth, and AMPAR localization at synapses. Live imaging of SEP-GluA1 and single-particle tracking revealed that Wnt7a rapidly promoted synaptic AMPAR recruitment and trapping. Wnt7a, through Fz7, induced CaMKII-dependent loss of SynGAP from spines and increased extrasynaptic AMPARs by PKA phosphorylation. We identify a critical role for Wnt-Fz7 signaling in LTP-mediated synaptic accumulation of AMPARs and spine plasticity.
Skin, the main barrier to the external environment, is subject to deterioration caused by dermatological disorders, environmental conditions and the intrinsic ageing process. This damage to both structure and function may be accelerated by smoking, alcohol consumption and chronic sun exposure (extrinsic components). All these factors may lead to the formation of wrinkles, the appearance of brown spots and skin thickening. One effective strategy to managing the skin ageing process is adopting a healthy nutritional approach to life, maintaining a balanced diet and a good supply of food supplements. This can restore the homeostasis of macro and micronutrients and support the physiology of cells and tissues in the skin. Hydrolysed collagen, an increasingly popular nutraceutical, is composed of low molecular weight small peptides, which are easily digestible, absorbed and distributed in the human body. Numerous clinical trials have now been performed showing the efficacy and benefits of collagen peptides on skin properties, such as hydration, elasticity and reduction of wrinkles. As a result, hydrolysed collagen can be considered an important weapon in the everyday fight against skin ageing.
Nutraceuticals containing collagen peptides, vitamins, minerals and antioxidants are innovative functional food supplements that have been clinically shown to have positive effects on skin hydration and elasticity in vivo. In this study, we investigated the interactions between collagen peptides (0.3–8 kDa) and other constituents present in liquid collagen-based nutraceuticals on normal primary dermal fibroblast function in a novel, physiologically relevant, cell culture model crowded with macromolecular dextran sulphate. Collagen peptides significantly increased fibroblast elastin synthesis, while significantly inhibiting release of MMP-1 and MMP-3 and elastin degradation. The positive effects of the collagen peptides on these responses and on fibroblast proliferation were enhanced in the presence of the antioxidant constituents of the products. These data provide a scientific, cell-based, rationale for the positive effects of these collagen-based nutraceutical supplements on skin properties, suggesting that enhanced formation of stable dermal fibroblast-derived extracellular matrices may follow their oral consumption.
daily oral consumption of the nutricosmeceutical. We also obtained a positive patient feedback through the self-assessment questionnaires. Taken together these results show that this nutricosmeceutical supplement may have photoprotective effects and help improve skin health.
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