Klaire Schott
Research Mentor(s): Elizabeth Litkowski
Mentor Department: Neurology
Authors:
Session: Session 2 (10:00am – 10:50am)
Presentation Type: Poster 75
Abstract
Abstract: Miglitol, an FDA-approved alpha-glucosidase inhibitor, is used to manage type II diabetes mellitus by preventing the breakdown of complex carbohydrates, thereby reducing postprandial hyperglycemia. Interestingly, Miglitol has been identified as aligning with the upregulated expression profile of excitatory layer 4/5 intratelencephalic (IT) neurons, which are critical for cognitive resilience (Telpoukhovskaia et al.). This connection suggests a potential role for miglitol in influencing cognitive function particularly in the context of Alzheimer’s disease (AD). Study Purpose: The overall study investigates the effect of miglitol treatment across a life-span on various strains, sexes, and genotypes in the genetically diverse AD-BXD mouse panel (N=650). The focus of this project is to evaluate food consumption across these factors. Recent findings (Tang et al.) have shown that alpha-glucosidase inhibitors, such as miglitol, can influence feeding behavior by altering glucose availability, leading to changes in dietary intake. Our aim is to evaluate feeding behavior in the context of genetic background. Methods: We assessed 6 AD-BXD strains: B6xBXD39, B6.5XFAD, B6xD2, B6xBXD125, B6xBXD62, B6xBXD152. We evaluated females in all 6 strains and males in 3 of the strains. Two genotypes, Ntg/Ntg (non-transgenic controls) and 5XFAD/Ntg (hemizygous transgenic AD models), were included. The 5XFAD mice carry transgenic APP and PSEN1 dominant mutations, leading to amyloid-beta plaque deposition, neuroinflammation, and cognitive deficits. Mice were divided into two dietary groups: control (standard mice chow) and test (miglitol-supplemented), with food consumption and weight monitored weekly and monthly. Mice were housed by sex and strain so that their food consumption can be assessed in accordance with these characteristics. Food intake was calculated by measuring the initial amount placed in the hopper and subtracting the remaining amount after one week. Results: Food consumption was measured over a 45-week period in NTg/NTg (control) and NTg/5xFAD (Alzheimer’s model) mice on either Chow or Miglitol diets. All groups initially demonstrated an increase in food intake, followed by a gradual decline and stabilization. This pattern was consistent across strains and genotypes; however, statistical analysis revealed significant treatment-related differences in food consumption in B6xBXD125 (Ntg/Ntg p = 0.0377; 5XFAD/Ntg p = 3.96 × 10?5) and B6xBXD62 (Ntg/Ntg p = 6.64 × 10?5). Similarly, significant effects were observed in the B6.5XFAD strain (Ntg/Ntg p = 0.00605; 5XFAD/Ntg p = 0.0097). No significant differences were detected in B6xBXD152 or B6xBXD39. However, when analyzed by sex within the B6xBXD39 strain, a significant treatment effect was observed in Ntg/Ntg females (p = 0.02), while Ntg/Ntg males (p = 0.755), 5XFAD/Ntg females (0.14), and 5XFAD/Ntg males (0.943) showed no significant differences. These findings suggest that Miglitol treatment modulates food consumption in a strain and genotype dependent manner, with notable effects in specific genetic backgrounds. Conclusion: These findings support prior research showing that while interventions like alpha-glucosidase inhibitors can initially alter feeding behavior, long-term intake normalizes — likely due to metabolic compensation. The persistent correlation between food intake and genotype highlights a potential confounding variable in behavioral or biochemical studies. Recognizing and accounting for this strengthens the validity of subsequent analyses by ensuring that observed outcomes are not driven by differences in food intake. Future: Preliminary analyses aim to determine whether strain, sex, or genotype influence dietary intake patterns in response to miglitol. The results will provide insight into the potential interaction between miglitol’s mechanism of action and dietary behavior. By repurposing miglitol, this research explores its therapeutic potential for addressing cognitive symptoms in neurodegenerative diseases, offering a promising avenue for clinical applications.
