CHEMOTHERAPY-INDUCED REMODELING OF CORTICAL PYRAMIDAL NEURONS: MORPHOLOGICAL EFFECTS OF OXALIPLATIN AND PACLITAXEL
Iezzi G1,2, Marmiroli P3,4, Vercelli A1,2 and Cavaletti G3,4 | 1Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy; 2Neuroscience Institute Cavalieri Ottolenghi,Turin, Italy; 3University of Milano-Bicocca, Italy; 4Experimental Neurology Unit, Monza, Italy
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Chemotherapy-induced neurotoxicity represents a limitation in cancer treatment, often leading to long-lasting sensory and cognitive disturbances. Oxaliplatin (OHP) and Paclitaxel (PTX) are two commonly used agents known for inducing peripheral neuropathy, yet growing evidence suggests they may also affect central neuronal circuits. This study investigates the impact of these drugs on cortical pyramidal neurons, aiming to identify structural correlates of chemotherapy-related cognitive impairment. Adult male Balb/c mice received intravenous injections of OHP (7 mg/kg/week, 8 weeks) and PTX at three different doses (5-7,5-10 mg/kg, 8 weeks), compared to vehicle-treated controls. Golgi-Cox staining was performed on brain tissue, and morphometric analyses were carried out on layer V pyramidal neurons in the somatosensory and prefrontal cortices using Neurolucida software. At the end of OHP treatment (T1), both cortical areas displayed reduced average dendritic length and branching, with preserved dendrite number. Spine density was maintained in the somatosensory cortex but shifted toward immature types, while the prefrontal cortex exhibited a reduction in spine number and mature (mushroom-type) forms. After 4 weeks of follow-up (T2), decrease in dendritic complexity and persistent spine immaturity were evident in both regions. Ongoing analyses on PTX-treated animals aim to define the dosedependent effects of this drug on cortical morphology. Preliminary observations suggest similar trends in dendritic and spine alterations, potentially with distinct regional or dose-related patterns. Overall, these findings indicate that both OHP and PTX induce structural remodeling of cortical pyramidal neurons, providing morphological evidence for central neurotoxicity associated with chemotherapy.
Supported by PRIN 2022 project 2022ZL4JP8 “Understanding and targeting CHEMOtherapy-related neuroTOXicity (CHEMOTOX)”.
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