Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

MiR-204-5p dysregulation is associated with FOXO1 expression and LC3II/I ratio in a Streptozotocin-induced rat model of Alzheimer’s disease

Articles in Press

Document Type : Original Article

Authors
Zahra Majdi 1
Leila Alidoust 2
Adele Jafari 1
Behrooz Khakpour-taleghani 1, 3
Mohammad Rostampour 3, 1
Kambiz Rohampour 4, 1
1 Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
2 Department of Genetics, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
3 Neuroscience Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
4 Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
10.22038/ijbms.2026.96924.20845
Abstract
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-204-5p and Forkhead box transcription factor O1 (FOXO1), as well as alterations in the LC3II/I ratio in a Streptozotocin (STZ)-induced rat model of AD.
Materials and Methods: Sixteen male Wistar rats (200-250 g) were randomly divided into control and Alzheimer’s model groups. An experimental model was induced by intracerebroventricular injection of STZ (3 mg/kg). Spatial and avoidance memory were assessed using the Y-maze and passive avoidance test. The expression levels of miR204-5p and FOXO1 were determined by real-time PCR, while the LC3II/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<0.0001). Molecular analyses demonstrated that miR-204-5p expression was significantly decreased in the brains of STZ-treated rats(P<0.05). Conversely, FOXO1 levels (P<0.01) and the LC3-II/LC3-I ratio (P<0.05) were significantly elevated compared to controls.
Conclusion: These findings suggest that altered miR-204-5p expression may be associated with increased FOXO1 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-204-5p/FOXO1 axis as a potential target for future mechanistic investigations.
Keywords
Alzheimer disease
Autophagy
FOXO1
LC3II/I ratio
MiR-204-5p
Streptozotocin
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 17 October 2026