en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Silver nanoparticles (AgNPs) have been shown to cross the blood&ndash;brain barrier (BBB) and induce neurotoxicity. In light of the widespread application of silver nanoparticles in industrial and medical fields, this study aimed to investigate the cerebellar toxicity of a newly developed silver nanostructure (alginate-coated silver nanostructures [Ag-NS]), focusing on their physicochemical characteristics and biological impact following acute and chronic exposure.&nbsp;<br> <strong>Methods</strong>: Au@Ag core&ndash;shell nanorods were synthesized and characterized. Forty male mice were randomly divided into five groups: a control group, two sham groups (administered alginate solution at 1.5 mg/kg/day for 14 and 35 days), and two treatment groups (administered Ag-NS at the same dose and durations). Cerebellar tissue was collected and analyzed for DNA fragmentation using the TUNEL assay. Gene expression levels of apoptotic (Bax, Bcl-2, and Caspase-3) and autophagy-related (LC3 and Beclin-1) genes were quantified using real-time PCR. Neuronal morphology was assessed via cresyl violet staining.&nbsp;<br> <strong>Results</strong>: High-resolution transmission electron microscopy (HR-TEM) analysis confirmed that the nanostructures were uniform, rod-shaped particles averaging approximately 60 nm in length. TUNEL staining revealed a significant increase in DNA fragmentation in Ag-NS-treated groups. Gene expression analysis showed upregulation of apoptotic markers and downregulation of autophagy-related genes. Histological examination revealed a marked increase in degenerated Purkinje cells (dark cells) in the treatment groups.<br> <strong>Conclusion</strong>: Exposure to alginate-coated Au@Ag nanorods induced significant cerebellar toxicity, particularly following chronic treatment, as evidenced by enhanced apoptosis and suppressed autophagy. These findings underscore the need for further studies to assess the safety of such nanostructures and optimize their design to minimize neurotoxic effects.&nbsp;</div> Silver nanostructures (Ag-NS), Neurotoxicity, Cerebellum, Apoptosis, Autophagy, Alginate coating 295 308 http://bcn.iums.ac.ir/browse.php?a_code=A-10-8379-1&slc_lang=en&sid=1 Mahsa Nazari mjnazari1368@gmail.com 13700319475328460058678 13700319475328460058678 No Department of Anatomy and Pathology, School of Medicine, Shahed University, Tehran, Iran. Ronak Shabani Shabani.r@iums.ac.ir 13700319475328460058679 13700319475328460058679 No Department of Anatomy, Reproductive Sciences and Technology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Maryam Akhavan Tavakoli maryam20005@gmail.com 13700319475328460058680 0009-0002-6659-2929 No Department of Anatomical Sciences, Cognitive Neurosciences, TeMS.C., Islamic Azad University, Tehran, Iran. Asghar Marzban Marzban.a@zums.ac.ir 13700319475328460058681 13700319475328460058681 No Department of Pediatrics, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. Sahar Eghbali Sahar.eghbali90@gmail.com 13700319475328460058682 13700319475328460058682 No Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Rana Mehdizadeh rana.mhdz@yahoo.com 13700319475328460058683 0009-0004-7808-028X No School of Dentistry, CT.C., Islamic Azad University, Tehran, Iran. Sahar Hakimpour sahar.hakimpour.ut@gmail.com 13700319475328460058684 13700319475328460058684 No Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. Mehdi Mehdizadeh Mehdizadeh.m@iums.ac.ir 13700319475328460058685 13700319475328460058685 Yes Department of Anatomy, Reproductive Sciences and Technology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.