Table 1.
WD effects on synaptic function and cognition in animals.
| Exp. Approach | Species, Sex, Age | Model | Learning/Memory | Synaptic Function, Neuroplasticity | Other Pathways | Refs. |
|---|---|---|---|---|---|---|
| Short periods (≤2 months) | ||||||
| Young animals | Rat (♀; 3 w) | CAFD (F/sucrose: 45%) & HFru solution (11%) or HFru solution alone vs. CD (F: 13.4% & C: 56.7%) for 5 w. Reversion: 5 w with CD | Impaired memory (novel object in context) at 5 w for CAFD and HFru solution. No reversion in CAFD group | - | Gut dysbiosis (before and after reversion) | [44] |
| Rat (♂; 6 w) | HFD-HDextrose (F: 41.7% & C: 36.7%) vs. CD (F: 13.5% & C: 58%) for 11 w | Impaired memory (NOR; no changes with MWM) | ↓ dendritic arborization in HPC neurons and ↑ in entorhinal cortex neurons | ↑ TNFα levels in blood | [45] | |
| Rat (♂; 6 w) | CAFD (cakes, biscuits & a protein source) & HSu solution (10%) vs. CD for 6 w | Impaired memory (NOR and NLR) | No changes in BDNF, TrkB and synapsin in HPC | ↑ inflammation and gut dysbiosis | [46] | |
| Rat (♀; 2 m) | HFD (F:39%) & refined sugar (40%) vs. CD (F: 13% & complex C: 59%) for 2 m | Impaired memory (MWM) | ↓ BDNF, phosphosynapsin I and phosphoCREB | - | [47] | |
| Adult animals | Rat (♂ and ♀; 9–10 w) | HFD (F: 60% & C: 20%) HFru solution (11%) vs. CD (F: 13% & C: 62%) for 6 w | Impaired hippocampal-dependent memory (NLR) in ♂ (no changes in ♀) | - | - | [48] |
| Rat (♂; adult) | CAFD (F: 45% & C: 50%) & HSu solution (10%) vs. CD (F: 15%, & C: 59%) for 5, 11 & 20 days | Impaired hippocampal-dependent memory (NLR; no changes in NOR) | No changes in BDNF | ↑ inflammation in HPC at 20 d | [49] | |
| Rat (♂) | CAFD (CD supplemented with cakes, biscuits & protein source) & HSu solution (10%) vs. CD for 5 w | Impaired memory (NLR) | - | Gut dysbiosis | [50] | |
| Rat (♂; adult) | HFD-HC (F: 25%, C: 44% & P: 18%) vs. CD (F: 5%, C: 62% & P: 18) for 6 w | Impaired short-term and long-term memory (RAWM) | No changes in BDNF | ↑ oxidative stress in HPC | [51] | |
| Rat (♂) | HFD (F: 40%, P: 5% & C: 15%) & HSu solution (40%) vs. CD (F: 15%, P: 25% & C: 55%) for 6 w. Reversion: 3 w with HFD-HSu and 3 w with CD and training | Impaired memory (NLR). Reversed by CD and training | - | - | [52] | |
| Rat (♂) | HFD (SFAs & MUFAs; 38%) & refined sugar (38%) vs. CD (F: 6% & sugar: 4.1%) for 8 w | Impaired memory (NOR) and learning (MWM) | ↓ GluA3 levels in dorsal HPC and altered levels in synaptic plasticity markers | Altered levels in energy metabolism markers (by proteomic analysis) | [53] | |
| Long periods (>2 months) | ||||||
| Young animals | Rat (♂; 21 days) | HFD (F: 29%, sucrose: 34% & cholesterol 1.25%) & HGlucose-HFru solution (55%/45%) vs. CD (F: 6% & C: 44%) for 8 m | - | ↓ PSD95 and BDNF, ↓ LTP in HPC | Gut dysbiosis, ↑ inflammation and microglia activation in HPC | [54] |
| Rat (♀; 1 m) | HFD (30% lard & 66% sucrose) & HSu solution (30%) vs. CD (F: 3%, C: 61% & P: 19%) for 24 m | Impaired memory (NOR) | ↓ TrKB, ↓ LTP in HPC | No changes in neurogenesis | [55] | |
| Rat (♂; 5–7 w) | HFD & HSu solution (5%) vs. CD for 4 m. Reversion: 3 m with bioactive food | Impaired spatial and working memory (T-maze and NOR). Reversed by bioactive foods | - | Gut dysbiosis. Reversed by bioactive foods | [56] | |
| Rat (♂; 6 w) | HFD-HFru (F: 30% & fructose: 15%) vs. CD for 6 m | Impaired learning (MWM) | - | ↑ BBB permeability, neurodegeneration and microglia activation | [57] | |
| Rat (♂; 6 w) | HFD-HFru (saturated F: 45% & fructose: 20%) vs. CD for 11 w | Impaired memory (NOR) | - | ↓ IGF1 and ↑ oxidative stress | [58] | |
| Mouse (♂; 6 w) | HFD-HSu (F: 60% & sucrose: 7%) vs. CD (F: 17%) for 13 w | Impaired memory (NOR) | ↓ GluA1, BDNF, phosphoCREB, TrkB in HPC and PFC | ↓ neurogenesis | [59] | |
| Mouse (♂; 7 w) | HFD (F: 40% & C: 20%) & HSu solution vs. CD (F: 12% & C: 67%) for 14 w | - | ↓ PSD95 and ↑ phosphoTau in brain (no changes in synaptophysin) | ↓ GLUT1/3, ↑ ER stress and inflammation responses and INS resistance in brain | [60] | |
| Rat (♂; 7 w) | CAFD (CD with cookies, cakes & biscuits) vs. CD once per day, 5 days per week for 5 m | - | ↑ BDNF and TrkB and ↓ phosphoTrkB in PFC. No changes in HPC | Redox imbalance | [61] | |
| Rat (♀; 8–10 w) | HFD (F: 40%, C: 45% & P 15%) & HFru solution (15%) vs. CD (F: 6%, C: 64% & P: 25%) for 12, 16 & 24 w | Impaired memory (MWM) at 16 and 24 w (no changes at 12 w) | - | ↑ oxidative stress and reduced antioxidant levels in HPC and CTX | [43] | |
| Rat (♂; 2 m) | HFD-HGlucose (F: 40%) vs. CD (F: 13%) for 3 m | Impaired learning (nonspatial discrimination learning problem) | - | ↑ BBB permeability in HPC | [62] | |
| Rat (♀; 2 m) | HFD (SFAs & MUFAs: 39%) & refined sugar (40%) vs. CD (F: 13% & C: 59%) for 1, 2 & 6 m or 2 y | Impaired learning and memory (MWM) at 1 and 2 m | ↓ BDNF and synapsin I in HPC | - | [63] | |
| Rat (♂; 2 m) | HFD (high-lard or high-olive oil) & HSu solution vs. CD for 10 w | No changes in spatial memory (Y-maze) | ↓ GluN2A in high-lard-HSu (no changes in high-olive oil-HSu) in CTX | - | [42] | |
| Rat (♂; 2 m) | HFD-HSu & HFru corn syrup solution (20%) vs. CD for 8 m | Impaired learning (MWM) | ↓ dendritic spine density, ↓ LTP and ↓ BDNF levels in CA1-HPC | - | [64] | |
| Mouse (♀ and ♂; 10 w) | HFD (F: 60%) & HSu solution (20%) vs. CD (F: 10%) for 4 or 6 m. Reversion: 8 w with CD | Impaired memory (NOR and NLR. No change in working memory (Y-maze). Recovered after 8 w of CD | ↑ microglia activation (no inflammation and neuronal loss). Recovered after 8 w of CD | [65] | ||
| Guinea pigs (♀; 10 w) | HFD-HSu (F: 20% & sucrose: 15%) vs. CD (F: 4% & sucrose: 0%) for 7 m | - | ↓ BDNF levels in HPC | - | [66] | |
| Rat (♂; adolescent) | HFD-HDextrose (SFAs: 41.7%) vs. CD (F: 13.4%) for 10 w | Impaired memory (NOR) | - | - | [67] | |
| Adult animals | Mouse (♂; 3 m) | HFD (F: 45%) & HFru solution (10%) vs. CD for 10 w | Impaired memory (MWM) | ↓ PSD95 and SNAP25 in HPC | INS resistance, ↑ microglia activation and inflammation in brain | [68] |
| Rat (♂) | HFD-HDextrose (F: 38%, P: 24%, C: 18% & dextrose: 20%) vs. CD (F: 18%, P: 24%, C: 58%) for 10, 40 & 90 days | Impaired learning at 10 and 90 d, no changes at 40 d (Y-shaped maze) | - | ↑ BBB permeability in HPC (only in obese rats) | [41] | |
| Mouse (♂; 3 m) | HFD-HFru (F: 48%, fructose: 33% & P: 19%) or HFD (F: 48%, C: 33% & P: 19%) vs. CD for 14 w | Impaired memory (NOR and NLR). HF-HFru more affected than HFD | ↓ glutamate and glutamine in HPC (no changes in GABA) | - | [69] | |
| Rat (♂) | HFD-HDextrose (F: 40%, P: 21% & C: 38%) or HFD-HSu (F: 40%, P: 21% & C: 38%) vs. CD (F: 12%, P: 28% & C: 59%) for 3 m | Impaired learning (nonspatial Pavlovian discrimination and reversal learning problem) | ↓ BDNF in prefrontal CTX and HPC with HF-HDextrose (no changes with HF-HSu) | - | [70] | |
| Rat (♂ and ♀) | HFD-HFru (CD: 60%, fructose: 30% & pork fat: 10%) vs. CD for 12 w | Impaired learning (MWM and passive avoidance test). ♂ more affected than ♀ | - | ↑ oxidative stress | [71] | |
| Short vs. long periods | ||||||
| Young animals | Mouse (♂; 6 w) | HFD-HFru (30% lard, 0.5% cholesterol and 15% fructose, all in weight/weight) vs. CD for 4 or 24 w | Impaired learning (MWM) at 14 w (no changes at 4 w) | - | ↑ BBB permeability and astrocytocis | [72] |
WD effects in animals were classified according to experimental approach, taking into account exposure time, short (≤2 months) or long (>2 months) periods, sex, and age classified as young and adult (≤2 months, >2 months). Search terms used were as follows: “western diet” OR “high fat” AND “sugar”, “sucrose”, “fructose” OR “dextrose” AND “memory”, “learning”, “synaptic plasticity” OR “AMPAR”. Only studies with rodents were included. Excluded were experimental models of maternal exposure, streptozotocin-treated animals, and pathological conditions. Percentage fats, carbohydrates, and proteins are relative to total energy unless otherwise indicated. Solution percentages are expressed as weight/volume unless otherwise indicated. Table symbols and abbreviations are as follows: ♀: female; ♂: male; ↑: increased; ↓: decreased; BBB: blood-brain barrier; BDNF: brain-derived neurotrophic factor; C: carbohydrates; CAFD: cafeteria diet; CD: control diet; CREB: cAMP response element-binding protein; CTX: cortex; ER: endoplasmic reticulum; F: fats; FC: fear conditioning; GABA: gamma-aminobutyric acid; GluA: AMPA receptor; GluN: NMDA receptor; GLUT: glucose transporter; h: hours; HC: high carbohydrate; HDextrose: high dextrose; HFD: high-fat diet; HFru: high fructose; HGlucose: high glucose; HPC: hippocampus; HSD: high-sugar diet; HSu: high sucrose; INS: insulin; IGF1: insulin-like growth factor 1; LTD: long-term depression; LTP: long-term potentiation; m: months; MUFAs: monounsaturated fatty acids; MWM: Morris water maze; NLR: novel location recognition; NOR: novel object recognition; P: protein; PFC: prefrontal cortex; phospho: phosphorylated; PSD95: postsynaptic density protein 95; PUFAs, polyunsaturated fatty acids; RAWM: radial arm water maze; SFAs: saturated fatty acids; SNAP25: synaptosomal-associated protein 25; SOLF: saturated oil-enriched food; TNFα: tumor necrosis factor; TrkB: tropomyosin receptor kinase B; UOLF: unsaturated oil-enriched food; vs.: versus; and w: weeks.