DUGi

Efectes d’un tractament d’estimulació elèctrica intracranial a llarg termini sobre els nivells hipocampals de proteïnes i miRNAs associats a plasticitat neural en rates model de malaltia d’Alzheimer

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@28680

Alzheimer’s disease (AD) is the leading cause of dementia worldwide and is characterized as a progressive and multifactorial neurodegenerative disorder that affects memory and learning. It has a greater impact on females, and evidence suggests that it affects men and women differently. This study investigates the sex-dependent effects of long-term intracranial electrical stimulation (ICSS) of the medial forebrain bundle (MFB) on the expression of specific proteins and miRNAs biomarkers in a sporadic AD animal model. The AD model was induced through an intracerebroventricular (ICV) injection of streptozotocin (STZ) and the MFBICSS therapy was administered for a total duration of 4 months. The study was conducted using 59 hippocampal samples, divided into six experimental groups based on sex and treatment received: Control, STZ, and STZ+ICSS. Protein expression levels of APP, pTAU, TAU, SIRT1, and DCX were analyzed using Western blot, and miRNA levels of miR-17, miR-191, and miR-let-7a were measured using RT-PCR. Regarding protein expression, results show that in male rats, ICV injection of STZ significantly increases pTAU and TAU levels while decreasing SIRT and DCX levels, suggesting neurodegeneration, loss of synaptic plasticity, and reduced neuroprotection and neurogenesis. In female rats, STZ only induces a significant increase in pTAU, with no relevant changes in the other proteins. The MFB-ICSS treatment restores SIRT1 levels in males but does not significantly alter other protein biomarkers. No treatment effects were observed on protein expression in female rats. As for miRNAs, in males, STZ significantly increases miR-17 expression, while in females no differences between groups were observed in any of the three miRNAs analyzed. The MFB-ICSS treatment does not improve the expression levels of the miRNAs in either sex. In conclusion, the results obtained from the ICV-STZ injection to model AD suggest a sex-specific response, with female rats showing a possible resistance to STZ-induced neurotoxicity. In contrast, male rats exhibit modulated expression levels of protein biomarkers, reflecting a profile similar to that of sporadic AD. The MFB-ICSS treatment demonstrates a neuroprotective effect in males by restoring SIRT1 expression levels. Lastly, the observed sex differences underscore the importance of incorporating a gender perspective in preclinical studies of neurodegenerative diseases such as Alzheimer’s disease

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