Table 2: Effects of diet on brain plasticity in animal studies of mood/anxiety from 2010 onwards.

ModelDietary factorInterventionCellular and molecular mechanismsEffects on behaviorConclusion/proposed mechanismReference

ICR strain male miceAcute fasting3 h, 9 h, and 18 h or
9 h + i.p. injection of IMI (30 mg/kg) or 9 h + i.p. injection of IMI
(30 mg/kg) + DOI (5 mg/kg)
↑ratio of p-CREB/CREB in 9 h fasting mice↓depressive-like behavior (FST) in 9 h fasting mice, which was more pronounced in 9 h + IMI. Effects reversed by DOIAntidepressant-like effects of acute fasting possibly occur via ↑p-CREB/CREB ratio, and additive effects with IMI via modulation of 5-HT2 receptors[111]

C57BL/6J mice 7-8
weeks of age
CRModerate 10–15% CR for 3 weeks
after CR, a subset of mice was refed either with a high-fat or chow diet AL
CR ↑stress-induced corticosterone levels,
↓BNST CRF levels and ↑BNST CRF promoter methylation
↑MCH and orexin among post-CR mice transitioned to high-fat diet
CR ↑depressive-like behaviour (TST)
↑binge eating of palatable high-fat foods after CR
MCH receptor-1 antagonist ↓total caloric intake in post-CR mice on high-fat diet
Moderate CR reprogrammes pathways involved in regulating stress responsivity and orexigenic drives.
Management of stress during diet may be beneficial in long-term maintenance

20–22 g male ICR miceTrans-RES10 mg/kg, 20 mg/kg, 40 mg/kg or 80 mg/kg via gavage, acute↑hippocampal 5-HT and ↓MAO-A activity (40 or 80 mg/kg)↓depressive-like behavior (FST: 20, 40, and 80 mg/kg; TST: 40 and 80 mg/kg)Antidepressant-like effects of trans-RES might be related, among others, to modulation of the 5-HT system[142]

180 g–200 g male Wistar ratsRES or UCMS + RES80 mg/kg, i.p., once daily for 5 weeksPrevented UCMS-induced ↑serum CORT, and ↓BDNF, pERK, and pCREB levels in the PFC and hippocampusPrevented UCMS-induced cognitive deficits (MWM; NORT)RES prevents UCMS-induced cognitive impairment partly via normalizing serum CORT levels and upregulating BDNF, pERK, and pCREB in the PFC and hippocampus[137]

200–250 g male Wistar ratsCUR or UCMS + CUR10 mg/kg via oral gavage, once daily for 3 weeksN/APrevented UCMS-induced depressive phenotype (SP; OFT)CUR exerts antidepressant effects partially by preventing UCMS-induced ↑of TNF- , IL-6, and NF- B in the PFC and hippocampus[183]

18–22 g male Kun-Ming miceTPs or UCMS + TPs25 mg/kg or 50 mg/kg by gavage once daily for 3 weeks from 3rd week on of UCMSReversed hippocampal and prefrontal cortex alterations of 5-HT and NEReversed UCMS-induced depressive-like behavior (FST, TST, SP, and OFT)Antidepressant action of TPs might be related to modulation of monoaminergic responses and ↑antioxidant defenses[143]

22–25 g male Kun-Ming miceRES or FLU20 mg/kg or 40 mg/kg or 80 mg/kg (RES); 10 mg/kg (FLU), i.p., once daily for 21 days↑BDNF and ERK levels in the hippocampus and PFC, ↓serum CORT↓depressive-like behavior (FST and TST)Antidepressant-like actions of RES are probably mediated by modulation of the HPA axis, BDNF, and Erk levels in the hippocampal and PFC[138]

190 g–200 g male Sprague-Dawley ratsTrans-RES10 mg/kg, 20 mg/kg, 40 mg/kg or 80 mg/kg via gavage 30 min before the chronic stress for 21 days↑5-HT levels in the frontal cortex, hippocampus, and hypothalamus (80 mg/kg); inhibited MAO-A activity in the frontal cortex and hippocampus (10–80 mg/kg)↓depressive-like behavior (SP and shuttle box test: 40 and 80 mg/kg)Antidepressant-like effects of trans-resveratrol involves, among others, the regulation of 5-HT levels and MAO-A activity[144]

8-9-month-old C57BL/6J and SIRT1 mutant miceRESIntraventricular injection of RES (5  g/ L for a week)↑LTP in CA1; ↑BDNF and CREB in hippocampal slices; ↓miR-134 and miR-124; effects blocked in SIRT1 mutant mice↑fear memory (contextual and tone-dependent memory test); effects blocked in SIRT1 mutant miceRES exerts its effects via regulation of microRNA-CREB-BDNF mechanism, likely in a SIRT1 dependent way[130]

3-4-month-old female Wistar rats and PND40 offspringRES or RES + CRS10 mg/kg orally administered throughout pregnancy↑hippocampal DCX and BDNFN/AResveratrol neuroprotects against prenatal stress likely via AHN improvement[140]

280–300 g female pregnant Sprague-Dawley rats; 15-week-old male offspringn-3 diet or n-3 defGestation, lactation, and postnatal week 15n-3 def ↓levels of DHA, NPY-1, BDNF and CREB; ↑GR in the frontal cortex, hypothalamus and hippocampusn-3 def ↑anxiety-like behavior in the OFT and EPMDHA deficiency during gestational and postnatal development ↓brain plasticity and compromises brain function in adulthood[184]

10-week-old virgin female
Wistar rats and PND90 male
FOAdaptation period (15 days), mating (8 days), pregnancy (21 days), and nursing (21 days)↑hippocampal and cortical BDNF; ↑hippocampal 5-HT↓depressive phenotype (FST); effects reversed by 5-HT1A antagonistn-3 PUFA exert antidepressant effects likely via increase in hippocampal 5-HT transmission[185]

6-month-old male Wistar ratsn-3 diet or n-3 def
or n-3 diet + CRS
or n-3 def + CRS
25 g/day from weaning to 3 months; 20 g/day until 6 months; CRS for 21 daysN/An-3 def ↓locomotor activity induced by CRS and ↑startle responsen-3 deficiency may contribute to vulnerability to stress[186]

280–300 g female pregnant Sprague-Dawley rats; 12-week-old male offspringDHA or HFDDHA = from gestation to postnatal week 15; HFD = DHA from gestation to postnatal week 12 + HFD until 15 weeksSwitch from DHA to HFD ↓DHA levels, NPY, BDNF, pCREB, GAP-43, pCAMKii, and p-syn expression in frontal cortex, and hippocampusSwitch from DHA to HFD ↓locomotor activity in the OPF and ↑anxiety-like behavior in one of the measures of the EPMTransition from DHA to HFD ↓plasticity markers and is associated with increased anxiety[187]

8-week-old BAFF TgPUFAs12 weeksPUFAs restored AHN and LTPN/APUFA can restore AHN in autoimmune mouse model[181]

Female Sprague-Dawley
rats and PND7 offspring
n-3 PUFAs (dam)
or n-3 PUFAs
(dam) + sevoflurane (offspring)
from pregnancy to PND14 (n-3 PUFAs); 6 h at PND7 (sevoflurane)n-3 PUFAs attenuated sevoflurane-induced neuronal apoptosis; ↑cell proliferation in the DGn-3 PUFAs restored fear response to footshock and ↑working and short-term memory (MWM)PUFA can improve altered memory and fear response in sevoflurane-treated rats via ↓apoptosis and ↑AHN[182]

280–300 g female pregnant Sprague-Dawley rats; 15-week-old male offspringn-3 diet or n-3 def
or n-3 diet + WD
or n-3 def + WD
or n-3 diet + WD + FPI
or n-3 def + WD + FPI
n-3 diet or n-3 def during brain maturation; WD for 6 weeks at 8 weeks of age n-3 def + WD disrupted BDNF signaling (TrkB, CaMKII, Akt, and CREB) and ↓NPY-1 in the frontal cortex; more pronounced after FPIn-3 def + WD ↑anxiety-like behavior (EPM); more pronounced after FPIn-3 def + transition to WD might lower the threshold for neurological disorders via BDNF and NPY-1 signaling disruption[188]

Effects of different proneural plasticity dietary interventions (CR, IF, and polyphenolic/fatty acid supplementation) on brain function and behavior in in recent animal studies (2010 onwards) of mood/anxiety. AHN: adult hippocampal neurogenesis; BDNF: brain-derived neurotrophic factor; BNST: bed nucleus of the stria terminalis; CORT: corticosterone; CREB: cAMP responsive-element binding; CRF: corticotropin-releasing factor; CRS: chronic restraint stress; CSA: continuous spontaneous alternation task; CUR: curcumin; DCX: doublecortin; DG: dentate gyrus; DHA: docosahexaenoic acid; DOI: serotoninergic 5-HT2A/2C receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride; EPM: elevated plus maze test; 5-HT: 5-hydroxytryptamine; 5-HT1A: 5-hydroxytryptamine type 1A receptor; FLU: fluoxetine; FO: fish oil-supplemented diet; FPI: fluid percussion injury; FST: forced swimming test; GAP-43: growth-associated protein 43; GR: glucocorticoid receptor; HFD: high fat diet; IL-6: interleukin 6; IMI: imipramine; i.p.: interaperitoneal injection; LTP: long term potentiation; MAO-A: monoamine oxidase-A; MCH: melanin-concentrating hormone (MCH); MWM: Morris water maze; N/A: not assessed; NE: noradrenaline; NF- B: nuclear factor kappa B; NORT: novel object recognition test; NPY-1: neuropeptide Y type 1 receptor; n-3 def: n-3 deficient diet; n-3 diet: n-3 adequate diet; OFT: open field test; p-CAMKii: Ca2+/calmodulin-dependent protein kinase II; pERK: phosphorylated extracellular signal-regulated kinase; PFC: prefrontal cortex; p-syn: phospho-synapsin; PUFA: polyunsaturated fatty acid-enriched diet; RES: resveratrol supplementation; SP: sucrose preference; TNF- : tumor necrosis factor alpha; TPs: tea polyphenols; Trans-RES: trans-resveratrol; TrkB: tyrosine kinase receptor B; TST: tail suspension test; UCMS: unpredictable chronic mild stress; WD: western diet.