MiR-۲۰۴-۵p dysregulation is associated with FOXO۱ expression and LC۳II/I ratio in a Streptozotocin-induced rat model of Alzheimer’s disease

Objective(s): Growing evidence suggests that dysregulated autophagy contributes to Alzheimer’s disease (AD) pathogenesis. MicroRNAs have emerged as important post-transcriptional regulators in neurodegenerative diseases. The present study investigated the expression of miR-۲۰۴-۵p and Forkhead box transcription factor O۱ (FOXO۱), as well as alterations in the LC۳II/I ratio in a Streptozotocin (STZ)-induced rat model of AD.Materials and Methods: Sixteen male Wistar rats (۲۰۰-۲۵۰ g) were randomly divided into control and Alzheimer’s model groups. An experimental model was induced by intracerebroventricular injection of STZ (۳ mg/kg). Spatial and avoidance memory were assessed using the Y-maze and passive avoidance test. The expression levels of miR۲۰۴-۵p and FOXO۱ were determined by real-time PCR, while the LC۳II/I ratio was assessed by Western blotting. Results: Behavioral assessments revealed significant memory deficits in STZ-treated rats, as indicated by reduced alternation percentage in the Y-maze and decreased step-through latency, accompanied by increased time spent in the dark compartment in the passive avoidance test (P<۰.۰۰۰۱). Molecular analyses demonstrated that miR-۲۰۴-۵p expression was significantly decreased in the brains of STZ-treated rats(P<۰.۰۵). Conversely, FOXO۱ levels (P<۰.۰۱) and the LC۳-II/LC۳-I ratio (P<۰.۰۵) were significantly elevated compared to controls.Conclusion: These findings suggest that altered miR-۲۰۴-۵p expression may be associated with increased FOXO۱ levels and potential autophagy-related changes in AD. These molecular alterations may contribute to autophagy-related changes associated with AD pathology and highlight the miR-۲۰۴-۵p/FOXO۱ axis as a potential target for future mechanistic investigations.

کلیدواژه ها:

Alzheimer disease ، Autophagy ، FoxO۱ ، LC۳II/I ratio ، MiR-۲۰۴-۵p ، Streptozotocin