Volume 30, Issue 3 (September 2026)                   Physiol Pharmacol 2026, 30(3): 364-376 | Back to browse issues page

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Ebadi A, moghimian M, eyzi S, saadatian Z, Alikhani V, soltani M. Effects of alkylating agents on hippocampal neuronal injury and miR-204-5p expression. Physiol Pharmacol 2026; 30 (3) :364-376
URL: http://ppj.phypha.ir/article-1-2668-en.html
Effects of alkylating agents on hippocampal neuronal injury and miR-204-5p expression
Amirhossein Ebadi , Maryam Moghimian , Samira Eyzi , Zahra Saadatian , Vida Alikhani , Malihe Soltani
Abstract:   (752 Views)

Introduction: The molecular mechanisms underlying chemotherapy-associated hippocampal neurodegeneration, particularly following exposure to alkylating agents, remain poorly understood. This study investigated the association between melphalan- and chlorambucil-induced hippocampal injury and alterations in the expression of apoptosis- and autophagy-related genes and miR-204-5p.
Methods: Adult male Wistar rats were treated daily for 30 days with saline (control), melphalan (Mel), or chlorambucil (Chl). Hippocampal tissue was analyzed using histological assessment of dark neurons and RT-qPCR analysis of apoptosis-related genes (Bax, Bcl-2, Caspase-3), autophagy-related genes (LC3β and Beclin-1), and miR-204 expression.
Results: Both Mel and Chl significantly increased the density of dark neurons in the hippocampus compared with the control group. Molecular analysis revealed increased mRNA expression of the pro-apoptotic genes Bax and Caspase-3 together with reduced expression of the anti-apoptotic gene Bcl-2. In addition, the expression levels of the autophagy-related genes LC3β and Beclin-1 were significantly decreased following treatment. Furthermore, miR-204 expression was significantly upregulated in both Mel and Chl groups and was accompanied by increased dark neuron density and coordinated alterations in the expression of apoptosis- and autophagy-related genes
Conclusion: These findings indicate that systemic exposure to melphalan and chlorambucil is associated with hippocampal neuronal injury, accompanied by altered expression of apoptosis- and autophagy-related genes. The consistent upregulation of miR-204 suggests that this microRNA may be associ-ated with the molecular changes observed following alkylating agent-induced hippocampal injury; however, further protein-level and functional studies are required to establish whether miR-204-5p plays a causal mechanistic role and to determine its potential therapeutic relevance in chemothera-py-associated neurotoxicity.

Keywords: Hippocampus, Neuronal injury, Melphalan, Chlorambucil, miR-204
Full-Text [PDF 704 kb]   (23 Downloads)    
Type of Manuscript: Experimental research article | Subject: Neurophysiology/Pharmacology
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