MOLECULAR AND BEHAVIORAL EFFECTS OF ACUTE DEHYDROEPIANDROSTERONE-SULFATE TREATMENT IN THE 3XTG MOUSE MODEL OF ALZHEIMER'S DISEASE

Aim: While DHEAS shows in vitro neuroprotection, its in vivo efficacy and dosing in Alzheimer’s disease (AD) remain unclear. Hypothesizing that its structure allows for long-lasting effects, we aim to characterize the behavioral and morphological impact of a single DHEAS injection in an AD model.
Methods: Seven-month-old male and female 3xTg-AD and wild-type control mice were treated intraperitoneally with DHEAS and compared to vehicle treatment (10mg\10mL/kg). To test learning and memory Y-maze and conditioned fear tests (CFT) were applied. After termination, qPCR technique was used to determine the differences in the levels of mAPP, hAPP, and Iba-1 expression.
Results: In the Y-maze, 3xTg-AD mice exhibited reduced locomotion but higher alternation, with females showing poorer working memory. CFT results showed that trauma and AD genotype both decreased exploration and increased freezing. The qPCR results confirmed human APP expression in 3xTg-AD mice, unaffected by trauma or DHEAS. However, the 3xTg-AD mice not only had higher mouse APP mRNA level, but DHEAS treatment showed a tendency (p=0.079) to reduce this level. The mRNA level of the microglia marker Iba-1 aimed to inform us about inflammatory processes increased by shock and there was a tendency for DHEAS to reduce this level (p=0.054) independently from genotype.
Conclusion: At behavioral level the single DHEAS injection 24h later was not able to correct behavioral alterations. However, there was a tendency to diminish neuroinflammation and amyloid accumulation. Further studies with alter timepoint are still needed to explore the full cognitive potential of DHEAS.