Table 1: Effects of diet on brain plasticity and cognition in animal studies from 2010 onwards.

ModelDietary factorInterventionCellular and molecular mechanismsEffects on behaviorConclusion/proposed mechanismReference

5-week-old male Wistar ratsEPA-E1.0 mg/g/day for 8 weeks via gavage↑LTP in CA1, ↑hippocampal p85αN/AEPA exerts neuroprotective effects via synaptic plasticity enhancement[176]

4-month-old obese and nonobese male Wistar rats60% CR10 weeks↑hippocampal NR2A and NR2B levels in CR obese rats; ↓MDA levels in all CR groupsN/ACR prevents oxidative stress, protecting NMDAR subunits 2A and 2B in obese rats which can result in ↑LTP and synaptic plasticity[49]

3-month-old female California mice80% CR8 weeks in SD or LD photoperiodNo CR-induced changes in hippocampal synapsin I or GFAP↓performance in LD mice in reversal learning (Barnes maze)Effects of CR on spatial learning are photoperiod dependent[48]

6-month-old BCKO mice70% CR5 weeks↓LTP in CR controls but not in BCKO↑memory and ↓aggressiveness in CR controls but not in BCKOCR effects depend on CREB-1 by its regulation of sirtuin transcription in neuronal cells[46]

12–14-week-old male SHRSP rats70% CR28 days or 28 days of
CR + EX training
↑hippocampal BDNF in
CR + EX rats
↑cognition (MWM) in
CR + EX rats
CR + EX act synergistically to upregulate BDNF and prevent cognitive decline in SHRSP rats[51]

~3-month-old male Sprague-Dawley ratsIF or ADX + IF or IF + KA or
ADX + IF + KA
14 weeks↓CA2/CA3 cell loss by IF and ADX + IF after KA insult; ↑BDNF and pCREB
in ADX + IF only
Attenuated KA-induced learning deficit in a T-maze task by ADX + IFIF protects hippocampal neurons against KA insult; IF effects are ↑under lower levels of CORT[107]

10–12-week-old male C57BL/6 mice; CGRP−/− miceRES20 mg/L orally administered once daily for 3 weeks↑hippocampal CGRP, IGF-I and IGF-I mRNA; ↑angiogenesis and AHN; no effects in CGRP−/− mice↑spatial learning (MWM); no effects on CGRP−/− miceRES stimulates sensory neurons in the GI tract, ↑IGF-I production and promoting angiogenesis and AHN, thereby ↑cognition[132]

38-month-old male grey mouse lemurs70% CR or RES70% CR or RES (200 mg/kg/day) for 18 monthsN/A directly; similar levels of serum CORT↑working memory (CSA); ↑spatial performance (CPT) only in RES groupCR and RES seem to induce similar benefits on cognitive functions in an adult primate by probably activating striatoprefrontal circuits and hippocampus[134]

10-week-old male Wistar ratsBlueberry2% for 7 weeksActivation of ERK1/2;
↑CREB; ↑pro- and mBDNF in the hippocampus; ↑BDNF mRNA in the DG and CA1
↑spatial learning in a delayed nonmatch task (8-arm maze)Flavonoid-rich blueberries ↑spatial learning in young healthy rats, likely through activation of ERK-CREB-BDNF pathway in the hippocampus[128]

8-week-old male Wistar ratsFlavonoids8.7 mg/day or 17.4 mg/day for 3 weeks↑PSA-NCAM in the DG and NMDA-NR2B in the hippocampus; ↑ERK/CREB/BDNF signaling, and ↑activation of the Akt/mTOR/Arc pathway↑spatial memory acquisition and consolidationFlavonoid-induced improvements in learning and memory might involve upregulation of PSA-NCAM and NMDA-NR2B[129]

10-week-old C57BL/6J female mice and PND19 male offspringALA or ALA-defGestation and/or lactationALA during gestation + lactation ↑cell proliferation and neuronal differentiation in the DG of PND19; ALA-def ↑apoptosisN/AALA is required in both fetal and postnatal stages for enhanced AHN in offspring[177]

Effects of different proneural plasticity dietary interventions (CR, IF, and polyphenolic/fatty acid supplementation) on brain function and cognition in recent animal studies (2010 onwards). ADX: adrenalectomy; ALA: -linolenic acid; BCKO: brain CREB knockout mice; BDNF: brain-derived neurotrophic factor; CGRP: calcitonin gene-related peptide; CORT: corticosterone; CR: calorie restriction; CREB: cAMP responsive-element binding; CSA: continuous spontaneous alternation task; DG: dentate gyrus; EPA-E: ethyl eicosapentaenoic acid; ERK 1/2: extracellular signal-related kinase 1/2; EX: exercise training; GI: gastrointestinal tract; IF: intermittent fasting; IGF-I: insulin-like growth factor-I; KA: kainic acid; LD: long day; LTP: long-term potentiation; mBDNF: mature form of BDNF; MDA: malondialdehyde; MWM: Morris water maze; N/A: not assessed; NMDAR: N-methyl-D-aspartate receptor; p-CREB: phosphorylated CREB; proBDNF: precursor form of BDNF; PSA-NCAM: polysialylated neural cell adhesion molecule; RES: resveratrol; SD: short day; SHRSP: stroke-prone spontaneously hypertensive rats.