Anthocyanins Promote Learning through Modulation of Synaptic Plasticity Related Proteins in an Animal Model of Ageing

Abstract

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 α-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.

Dietary polyphenols and their relationship to the modulation of non-communicable chronic diseases and epigenetic mechanisms: A mini-review

“… Activation of ERK-CREB-BDNF pathway; ↑ Spatial and psychomotor performances in aged rats; modulation of key synaptic proteins. ( Vauzour et al, 2021 ) Luteolin-7-O-glucoside (LUT-7G) Neuroprotection PD models:SH-SY5Y cells and C57BL6 (male) mice aged 20 weeks treated with LUT-7G treated for 15 days. NE ↑ Bcl-2/Bax ratio, ↓ Expression of cleaved caspase 3 ↑ ERα and Erβ expression, ↑ ERK1/2/STAT3/c-Fos activatipn, ↑Muscle strength, ↓ MPTP-induced gliosis in substantia nigra, ↑ TH positive nerve fibers in striatum.…”

Behind the Scenes of Anthocyanins—From the Health Benefits to Potential Applications in Food, Pharmaceutical and Cosmetic Fields

“…In addition, the bioinformatic analyses proposed that the identified 1698 differentially expressed genes could be involved in numerous cellular and molecular processes, comprising inflammation, neuronal function, metabolic processes, and signal transduction, which are involved in cognitive function and neurodegenerative disorders (e.g., Alzheimer’s, Parkinson’s disease). Furthermore, Vauzour et al [ 115 ] elucidated the underlying mechanisms of actions associated with anthocyanin-rich extract, specifically neuronal signalling, and synaptic function/integrity. The results suggest that the consumption of anthocyanin-rich extract improves learning capabilities in aged rats, counteracting spatial memory loss in aged brains, through the modulation of several cell signalling events implicated predominantly in synaptic plasticity, apoptosis, and cytoskeleton remodelling.…”

“…The results suggest that the consumption of anthocyanin-rich extract improves learning capabilities in aged rats, counteracting spatial memory loss in aged brains, through the modulation of several cell signalling events implicated predominantly in synaptic plasticity, apoptosis, and cytoskeleton remodelling. These behavioural variations are complemented by a regional rise of brain-derived neurotrophic factor mRNA expression within the hippocampus, highlighting a possible mechanism of action attributable to the memory enhancements detected in the aged animals [ 115 ].…”

Enhancing the Cognitive Effects of Flavonoids With Physical Activity: Is There a Case for the Gut Microbiome?

“…Blueberry-supplemented rats demonstrated elevated hippocampal levels of cAMP-response element-binding protein and extracellular signal-related kinase, and brain-derived neurotrophic factor (BDNF) compared to age-matched controls. Alteration of these signaling proteins led to better performance on a spatial working memory task ( Williams et al, 2008 ; Vauzour et al, 2021 ). BDNF, known for differentiation and survival of neurons of the CNS, plays a crucial role in delay of cognitive aging by improving hippocampal plasticity, long-term memory, and neurogenesis ( Cunha et al, 2010 ).…”