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This work was funded by the Catalan Government (2021SGR01214), MICIU/AEI PID2019-106332GB-I00 and PID2022-141252NB-I00 under "ERDF A way of making Europe", and MCIN/AEI PID2021-122636OB-I00 under ERDF "A way of making Europe". M. B.-S. has been supported by the Research Grant [FI, 2021-FI-B00755 Agencia de Gestio d'Ajuts Universitat i Recerca (AGAUR)], A. P. by the Spanish Ministerio de Ciencia Innovacion y Universidades (grant no. PRE2020-092084, project no. PID2019-106332GB-I00), M. J.-E. by Universitat Rovira i Virgili (grand no. 2023PMF-PIPF-15) and V. C. M. by a research contract from the project PID2019-106332GB-I00 under the collaboration framework agreement between the Diputacio de Tarragona and the Universitat Rovira i Virgili for the period 2020-2023 with the reference number 2022/07: "Els antioxidants derivats de les llavors del raim com molecules preventives en l'envelliment del sistema neuromuscular". We would like to express our heartfelt gratitude to Dr Neus Garcia, whose contribution played a vital role in developing our research. She will always be remembered and missed. This work is dedicated to her memory. We thank Dr Carme Grau-Bove for animal care and technical support.

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Protective effects of grape seed procyanidin extract on neurotrophic and muscarinic signaling pathways in the aging neuromuscular junction

Publicat a:Food & Function. 16 (9): 3575-3590 - 2025-04-15 16(9), DOI: 10.1039/d5fo00286a

Autors: Balanyà-Segura M; Polishchuk A; Just-Borràs L; Cilleros-Mañé V; Silvera C; Jami-ElHirchi M; Pinent M; Ardévol A; Tomàs M; Lanuza MA; Hurtado E; Tomàs J

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At the neuromuscular junction (NMJ), which coordinates movement, postsynaptic-derived neurotrophic factors have neuroprotective functions and retrogradely regulate the exocytotic machinery involved in neurotransmitter release. In parallel, presynaptic autocrine muscarinic signaling plays a fundamental modulatory role in this synapse. We previously found that these signaling pathways are impaired in the aged neuromuscular system. In this follow-up study, we investigated an anti-aging strategy using grape seed procyanidin extract (GSPE), a common dietary antioxidant known for its neuroprotective properties in various pathologies, but its effects on the aged neuromuscular system remain unexplored. This study analyses whether GSPE can mitigate age-associated impairments in neurotrophic and muscarinic signaling within the neuromuscular system. We assessed the expression (protein levels) and activation (phosphorylation) of the key proteins in the brain-derived-neurotrophic-factor (BDNF)/neurotrophin 4 (NT-4) and muscarinic pathways in the extensor digitorum longus (EDL) muscles of aged rats, with comparisons to GSPE-treated aged rats and young controls. The results demonstrate that GSPE treatment prevents the most relevant aging-induced changes in neurotrophic and muscarinic receptor isoforms, downstream protein kinases, and their targets in the neurotransmitter exocytotic machinery. Nevertheless, GSPE was less effective at preventing alterations in some other proteins within these pathways, such as calcium channels, and did not modify several other molecules involved in these pathways, which remain unchanged during aging. Overall, this study highlights the neuroprotective potential of GSPE in preventing fundamental age-related molecular changes at the NMJ, which helps improve functionality and may increase the quality of life and lifespan in aged individuals.

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