Effect of astaxanthin in type-2 diabetes -induced APPxhQC transgenic and NTG mice

• DOI: 10.1016/j.molmet.2024.101959
• Publication Date: 2024-05-17T17:10:04Z
• Authors: Joshua Adekunle B...; Anika Stracke; Tina Loeffler; Irene Schilcher; Spyridon Sideromenos; Stefanie Flunkert; Joerg Neddens; Ake Lignell; Manuela Prokesch; Ute Pazenboeck; Herbert Strobl; Jelena Tadic; Gerd Leitinger; Achim Lass; Birgit Hutter-Paier; Gerald Hoefler
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Amyloid beta-Peptides; Pyroglutamylation; Astaxanthin; Metabolic perturbation; Type 2 diabetes; Mice, Transgenic; Alzheimer's disease; Xanthophylls; Diet, High-Fat; RC31-1245; Mice, Inbred C57BL; Mice; Amyloid beta-Protein Precursor; Diabetes Mellitus, Type 2; Alzheimer Disease; Animals; Humans; Original Article; Internal medicine

Aggregation and misfolding of amyloid beta (Aβ) tau proteins, suggested to arise from post-translational modification processes, are thought be the main cause Alzheimer's disease (AD). Additionally, a plethora evidence exists that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), dyslipidemia pathogenesis AD. We thus investigated combinatory effect T2D human glutaminyl cyclase activity (pyroglutamylation), on pathology AD whether astaxanthin (ASX) treatment ameliorates accompanying pathophysiological manifestations. Male transgenic mice, APPxhQC, expressing APP751 with Swedish London mutation (hQC) enzyme their non-transgenic (NTG) littermates were used. Both APPxhQC NTG mice allocated 3 groups, control, T2D-control, T2D-ASX. Mice fed control or high fat diet ± ASX for 13 weeks starting at an age 11-12 months. High further treated streptozocin induction. Effects genotype, induction, evaluated by analysing glycemic readouts, lipid concentration, Aβ deposition, hippocampus-dependent cognitive function nutrient sensing using immunosorbent assay, ELISA-based assays, western blotting, immunofluorescence staining, behavioral testing via Morris water maze (MWM), respectively. presented higher glucose sensitivity compared mice. T2D-induced brain dysfunction was more severe in induction impaired memory functions while increasing hepatic LC3B, ABCA1, p65 levels resulted progressive shift soluble insoluble form reversed T2D- induced parallel increased pAKT decreasing cerebral p-S6rp levels. reduced Aβ38 Aβ40 demonstrate poses additional risk seen deposition. Although expression rescued impairment alone may not effective cases comorbidity