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Neurodegeneration, trauma and stroke – MNESYS
Funding: PNRR
The present study used dopaminergic cell cultures to investigate toxic effects and underlying mechanisms of mitochondrial toxin-induced neuronal cell death rotenone as an in vitro model for the study of parkinson's disease A 24-hour incubation with rotenone on PC12 dopaminergic cells affects the ultrastructure cellular, by causing a decrease in synaptic vesicles, induces a decrease in cell viability, resulting in an increase in ROS production and release and an increase in the number of cells subject to apoptosis. A reduction in dopamine release has also been observed due to the alteration of the mechanisms underlying the vesicular exocytosis functions. The study then continued to analyze the dopaminergic neurons differentiated starting from from PC12 cells. During the project, morphological changes in labeled cells were evaluated neuronal molecular markers. We also confirmed that incubation with rotenone at a concentration of 0.5 uM is the main dose that causes damage to neuronal viability, while maintaining minimal physiological neuronal status. A detailed series of electrophysiological, morphological and biochemical studies was conducted to characterize in a way delve deeper into this cellular model. To evaluate complete neuronal maturation also from the point of view electrophysiological, dopaminergic neurons were evaluated using high-density MEA multielectrode recordings with 4000 electrodes, where diffuse and distributed synaptic activation activity was detected, absent before the protocol of differentiation, monitored over the entire recording area of the chip. Our research team was also involved in the analysis of serum derived from stroke patients and their respective patients controls, in in vitro electrophysiological recordings. The main objective of the analysis is to demonstrate neuronal effects and molecular of possible inflammatory biomarkers to be translated into clinical studies.
The present molecular and electrophysiological study confirmed the full validity of the in vitro model of differentiation neuronal starting from PC12 neuroblastoma cells, thus providing us with a more than valid model for future studies on neuronal toxicity and for the study of sera taken from both parkinsonian patients and stroke patients analyzed with neurochemical techniques (luminex) to evaluate their inflammatory cytokine content. This study will provide important cellular and molecular information for the implementation of new therapeutic approaches.
TRL: 1
Spoke 6 : Neurodegeneration, Trauma and Stroke
