DHA supplementation, either from fish oil or DHASCO oil, showed retinal protective effects in 5xFAD Alzheimer's mice, underscoring the potential of retinal biomarkers as non-invasive indicators of cognitive decline and overall brain health.
Key Findings
Results
No statistically significant differences in retinal layer thicknesses were observed across dietary groups in 5xFAD mice.
Forty 5xFAD transgenic male mice aged five weeks old were distributed across five dietary groups (n=8 each) and fed isocaloric diets for 6 months.
Retinal layer thicknesses were measured across all groups including control, LSO, FO, Schizo, and DHASCO diets.
p > 0.05 for all retinal layer thickness comparisons across diets.
Despite lack of statistical significance, a consistent pattern of slightly increased retinal thickness was observed in 5xFAD mice fed fish oil relative to the other groups.
Results
Fish oil-fed 5xFAD mice showed a consistent pattern of slightly increased thickness across multiple specific retinal layers compared to other dietary groups.
The pattern was observed for total retinal layers as well as specific layers including the inner segment/outer segment layer, outer nuclear layer, outer plexiform layer, inner nuclear layer, and inner plexiform layer.
This pattern was consistent but did not reach statistical significance (p > 0.05).
Fish oil diet was supplemented with 2% cod liver oil, rich in both DHA and EPA (20:5n-3).
Results
Ganglion cell layer (GCL) density was significantly increased in 5xFAD mice fed the DHASCO oil diet compared to control.
The DHASCO diet contained 2% supplementation with a commercial oil containing 70% DHA.
p < 0.05 for GCL density comparison between DHASCO and control groups.
The increased GCL density suggests a benefit of DHA supplementation on the number of viable ganglion cells.
No significant differences in GCL density were reported for other dietary groups (LSO, FO, Schizo) relative to control.
Results
No positive staining was observed for β-amyloid plaques deposition or the neuroinflammatory marker IBA1 in the retinas of 5xFAD mice.
Immunohistochemical staining was performed for β-amyloid plaques deposition, TAU protein levels, and IBA1 across all dietary groups.
The absence of β-amyloid and IBA1 staining corroborates previous findings in human AD retinas.
This finding applied across all five dietary groups regardless of DHA supplementation type.
Results
Intense TAU immunostaining was observed in the internal retinal layers of 5xFAD mice.
TAU immunostaining was identified as a hallmark feature of AD progression in the retina.
Intense TAU immunostaining was specifically localized to the internal retinal layers.
TAU immunostaining was assessed both as immunostained area and number of TAU-positive cells.
Results
TAU immunostained area was significantly reduced in 5xFAD mice fed a fish oil diet compared to control, though the number of TAU-positive cells did not differ across diets.
p < 0.05 for TAU immunostained area comparison between fish oil and control groups.
The number of TAU-positive cells did not differ across diets (p > 0.05).
Fish oil diet was supplemented with 2% cod liver oil rich in both DHA and EPA.
No other dietary group showed a statistically significant reduction in TAU immunostained area relative to control.
Methods
The study used five dietary groups in 5xFAD transgenic mice to compare different DHA sources including non-fish environmentally friendly sources.
Dietary groups included: control (no supplementation), linseed oil (LSO, rich in ALA 18:3n-3), cod liver oil (FO, rich in DHA and EPA), Schizochytrium sp. microalga oil (Schizo, 40% DHA), and commercial DHASCO (70% DHA).
Each supplemented diet contained 2% of the respective lipid source in an otherwise isocaloric AIN-93M standard formulation.
Animals were fed for 6 months starting at five weeks of age.
All groups had eight animals each (total n=40 5xFAD transgenic male mice).