2026-04-04T02:25:27Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/276532026-03-07T07:57:50Zcom_2072_452955com_2072_2054col_2072_452958

00925njm 22002777a 4500 dc Riberas Sánchez, Andrea author Puig Parnau, Irene author Vila-Solés, Laia author García-Brito, Soleil author Aldavert Vera, Laura author Segura Torres, Pilar author Huguet i Blanco, Gemma author Kádár García, Elisabeth author 2024-03-15 Background: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is on-going. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. Methods: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-β precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. Results: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin with-out MFB-ICSS. Limitations: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. Conclusion: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits This work was supported by grants PID2020-117101RB-C21 and PDI2020-117101RB-C22 from the Ministerio de Ciencia eInnovación, Spain. Andrea Riberas-Sánchez received a predoctoralfellowship from the Universitat de Girona (IFUdG2022/63) Neurociències Neurosciences Alzheimer, Malaltia d' Alzheimer's disease Cervell -- Estimulació Brain stimulation Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease