GSPE pre-treatment protects against long-term cafeteria diet-induced mitochondrial and inflammatory affectations in the hippocampus of rats

ABSTRACT

Deregulations like the loss of sensitivity to insulin (insulin resistance) and chronic inflammation are alterations very commonly found in sporadic forms of neurodegenerative pathologies. Thus, finding strategies to protect against them, may lead to a reduction in the incidence and/or affectation of these pathologies. The grape seed-derived proanthocyanidins extract (GSPE) is a mixture of compounds highly enriched in polyphenols and flavonoids that have shown to have a wide range of therapeutic benefits due to their antioxidant and anti-inflammatory properties.

Objectives

This study aimed to assess the protective effects of a short pre-treatment of GSPE in the hippocampus against a prolonged feeding with cafeteria diet.

Methods

GSPE was administered for 10 days followed by 12 weeks of cafeteria diet. We analyzed transcriptional activity of genes and protein expression of key mediators of neurodegeneration in brain samples.

Results

Results indicated that GSPE was able to protect against cellular damage through the activation of AKT, as well as promote the maintenance of mitochondrial function by conserving the OXPHOS complexes and upregulating the antioxidant SOD.

Discussion

We observed that GSPE decreased inflammatory activation as observed through the downregulation of JNK, IL6 and TNFα, just like the reduction in reactive profile of astrocytes. Overall, the data presented here offers an interesting and hopeful initial step for future long-term studies on the beneficial effects of a supplementation of common diets with polyphenol and flavonoid substances for the amelioration of typical early hallmarks of neurodegeneration.

KEYWORDS:

• GSPE
• metabolism
• cafeteria
• diet
• hippocampus
• brain
• stress
• inflammation

Acknowledgements

MP is a Serra Húnter fellow. We would like to express our thanks to Niurka Llópis for her technical support.

Author contributions

Conceptualization, M.P.; E.R.-G.; O.B.; J.F.; A.C.; Methodology and Investigation, O.B.; J.F.; E.V.; Data Curation, O.B.; Resources, M.E.; Formal analysis, O.B.; T.E.-J.; M.C.; Writing – Original Draft Preparation, O.B.; M.P.; J.F.; Writing – Review & Editing, O.B.; E.R.-G.; M.P.; Visualization, Supervision, T.C.; J.T.; Project Administration, O.B.; M.E.; M.B.; Funding Acquisition, M.P.; T.C.; C.A.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The research group is partly supported by funds from the Ministerio de Economía, Industria y Competitividad, Gobierno de España [SAF2017-84283-R to AC; AGL2017-83477-R to MP], the Generalitat de Catalunya [2014SGR-525 to AC] [2017 SGR 625 to CA] and CIBERNED [Grant CB06/05/2004 to AC].