Related Experiment Video
Updated: Aug 6, 2026
An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment
Published on: April 20, 2018
Multimodal characterization of age-dependent susceptibility to high-cholesterol-diet-induced AD-like alterations in
NingBo Yin1, Honglei Ding2, Ruisi Su1
1Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, China; The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Abstract:
Rabbit models induced by a high-cholesterol diet can exhibit Alzheimer's disease (AD)-like neuropathological features, but susceptibility to diet-induced pathological alterations may vary with age and strain. This study aimed to investigate age-dependent susceptibility to high-cholesterol-diet-induced AD-like alterations in white-haired and black-eyed (WHBE) rabbits using a multimodal approach. Compared with the normal control group (NC), juvenile rabbits (2 months old) in the 2% high-cholesterol diet (CD) group showed disturbed plasma lipid and glucose metabolism, increased body weight, and reduced encephalization quotient (EQ). Neuropathologically, juvenile CD rabbits exhibited enhanced hippocampal Tau hyperphosphorylation and Aβ deposition. MRI demonstrated significant hippocampal atrophy and lateral ventricular enlargement, while 1H-MRS revealed significant reductions in hippocampal N-acetylaspartate/Cr, glutamate (Glu)/Cr, and glycerophosphocholine (GPC) + phosphocholine (PCH)/Cr ratios. In the overall cohort, Tau protein expression was negatively correlated with (Glu + Gln)/Cr (rho = -0.50, P = 0.0096) and positively correlated with (GPC + PCH)/Cr (rho = 0.42, P = 0.0167), although these correlations lost significance after FDR correction in subgroup analyses. Additionally, Aβ expression was negatively correlated with age in pooled WHBE rabbits (rho = -0.35, P = 0.0437), with no significant metabolite correlations observed after multiple testing correction. Multiple linear regression further confirmed a significant 'Diet×Age' interaction for both Tau and Aβ, indicating the pathological effect of high-cholesterol diet was most prominent in juvenile animals. These findings suggest that juvenile WHBE rabbits are more vulnerable to high-cholesterol-diet-induced AD-like changes. This study provides a multimodal reference for optimizing rabbit AD models and exploring age-related neurodegenerative vulnerability.
