STZ‑induced sporadic Alzheimer's in rats: behavioral, histopathological, and MiRNA profiles

Alzheimer's disease (AD) is a multifactorial disease, resulting from a combination of environmental and genetic predisposing factors, leading to the build-up of Amyloid (Aβ) plaques and tangles of phosphorylated Tau (p-Tau). MicroRNAs such as Let-7 s have been shown to exert neurotoxic effects. MiR-107 endogenously suppresses Let-7 s, and it was found to be downregulated in the brains of AD patients. However, miR-107 expression in the hippocampus in the STZ-induced sAD model has yet to be investigated. Thus, the current study aimed to investigate the levels of selected Let-7 s and miR-107 in the acute and chronic phases of STZ-induced sAD in rats. Adult Sprague-Dawley rats were subdivided into 6 groups: young intact, young vehicle control (CSF), acute STZ, old intact, old CSF, and chronic STZ. sAD was induced by stereotaxic injection of STZ in the lateral ventricles. The acute STZ group and age-matched controls were tested 4 weeks after STZ injection, while the chronic STZ group and age-matched controls were tested 13 weeks after the injection. Results showed reductions in cognitive and locomotor activities along with increased anxiety-related behaviors in the STZ-model groups in the open-field tests and T-maze tests. P-Tau was elevated in the STZ groups and old controls, with the chronic STZ group having the highest concentration. Let-7 miRNAs did not exhibit any change in expression in any group, while miR-107 was upregulated in the STZ-model groups. There was a negative correlation between miR-107 fold change and the behavioral changes and positive correlation between miR-107 fold change and anxiety-related behaviors. Histopathological examination revealed AD-like neurodegenerative changes in the hippocampi of STZ-model rats. These results further confirm the evidence implicating miR-107 expression in AD pathogenesis.