PMID- 34439483 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220522 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 10 IP - 8 DP - 2021 Jul 31 TI - Anthocyanins Promote Learning through Modulation of Synaptic Plasticity Related Proteins in an Animal Model of Ageing. LID - 10.3390/antiox10081235 [doi] LID - 1235 AB - Anthocyanin-rich foods, such as berries, reportedly ameliorate age-related cognitive deficits in both animals and humans. Despite this, investigation into the mechanisms which underpin anthocyanin-mediated learning and memory benefits remains relatively limited. The present study investigates the effects of anthocyanin intake on a spatial working memory paradigm, assessed via the cross-maze apparatus, and relates behavioural test performance to underlying molecular mechanisms. Six-week supplementation with pure anthocyanins (2% w/w), administered throughout the learning phase of the task, improved both spatial and psychomotor performances in aged rats. Behavioural outputs were accompanied by changes in the expression profile of key proteins integral to synaptic function/maintenance, with upregulation of dystrophin, protein kinase B (PKB/Akt) and tyrosine hydroxylase, and downregulation of apoptotic proteins B-cell lymphoma-extra-large (Bcl-xL) and the phosphorylated rapidly accelerated fibrosarcoma (p-Raf). Separate immunoblot analysis supported these observations, indicating increased activation of extracellular signal-related kinase (ERK1), Akt Ser473, mammalian target of rapamycin (mTOR) Ser2448, activity-regulated cytoskeleton-associated protein (Arc/Arg 3.1) and brain-derived neurotrophic factor (BDNF) in response to anthocyanin treatment, whilst alpha-E-catenin, c-Jun N-terminal kinase (JNK1) and p38 protein levels decreased. Together, these findings suggest that purified anthocyanin consumption enhances spatial learning and motor coordination in aged animals and can be attributed to the modulation of key synaptic proteins, which support integrity and maintenance of synaptic function. FAU - Vauzour, David AU - Vauzour D AUID- ORCID: 0000-0001-5952-8756 AD - Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK. FAU - Rendeiro, Catarina AU - Rendeiro C AD - School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. FAU - D'Amato, Alfonsina AU - D'Amato A AUID- ORCID: 0000-0002-8147-7235 AD - Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy. FAU - Waffo-Teguo, Pierre AU - Waffo-Teguo P AD - UFR des Sciences Pharmaceutiques, Unite de Recherche OEnologie EA 4577, University of Bordeaux, USC 1366 INRA, Equipe Molecules d'Interet Biologique, 210 Chemin de Leysotte, F-33882 Villenave d'Ornon, France. FAU - Richard, Tristan AU - Richard T AUID- ORCID: 0000-0002-5308-8697 AD - UFR des Sciences Pharmaceutiques, Unite de Recherche OEnologie EA 4577, University of Bordeaux, USC 1366 INRA, Equipe Molecules d'Interet Biologique, 210 Chemin de Leysotte, F-33882 Villenave d'Ornon, France. FAU - Merillon, Jean Michel AU - Merillon JM AD - UFR des Sciences Pharmaceutiques, Unite de Recherche OEnologie EA 4577, University of Bordeaux, USC 1366 INRA, Equipe Molecules d'Interet Biologique, 210 Chemin de Leysotte, F-33882 Villenave d'Ornon, France. FAU - Pontifex, Matthew G AU - Pontifex MG AD - Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK. FAU - Connell, Emily AU - Connell E AD - Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK. FAU - Muller, Michael AU - Muller M AUID- ORCID: 0000-0002-5930-9905 AD - Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK. FAU - Butler, Laurie T AU - Butler LT AD - Faculty of Science and Engineering, Anglia Ruskin University, Cambridge CB1 1PT, UK. FAU - Williams, Claire M AU - Williams CM AUID- ORCID: 0000-0003-4452-671X AD - School of Psychology and Clinical Language Sciences, University of Reading, Reading RG6 6AL, UK. FAU - Spencer, Jeremy P E AU - Spencer JPE AD - Molecular Nutrition Group, Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP, UK. LA - eng GR - BB/F008953/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article DEP - 20210731 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC8388918 OTO - NOTNLM OT - brain OT - cognition OT - flavonoids OT - neuroprotection OT - signalling COIS- The authors declare no conflict of interest. EDAT- 2021/08/28 06:00 MHDA- 2021/08/28 06:01 PMCR- 2021/07/31 CRDT- 2021/08/27 01:04 PHST- 2021/06/04 00:00 [received] PHST- 2021/06/30 00:00 [revised] PHST- 2021/07/23 00:00 [accepted] PHST- 2021/08/27 01:04 [entrez] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/08/28 06:01 [medline] PHST- 2021/07/31 00:00 [pmc-release] AID - antiox10081235 [pii] AID - antioxidants-10-01235 [pii] AID - 10.3390/antiox10081235 [doi] PST - epublish SO - Antioxidants (Basel). 2021 Jul 31;10(8):1235. doi: 10.3390/antiox10081235.