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Poster De Conférence Année : 2022

Functional integration of intranigral grafted hiPSC derived dopamine neurons in a mouse model of Parkinson disease

Résumé

Mainly characterized by a progressive degeneration of mesencephalic dopaminergic (DA) neurons of the substancia nigra pars compacta (SNc), Parkinson's disease (PD) induces major imbalances of basal ganglia loop activity resulting mainly in motor symptoms. Therapeutic proposals are multiple but among the most promising ones, the cell therapy is emerging as a major research axis. In this context, we propose to study the functional integration of an intranigral graft of DA progenitor neurons derived from human induced-pluripotent stem cells (DA-hiPSCs) in 6-OHDA RAG2-KO mouse model of PD.
Nine months after 6-OHDA lesion and transplantation, we investigated the electrophysiological functionality of the identified grafted-DA neurons by performing unit extracellular recordings in anesthetized mice to compare their electrophysiological characteristics to SNc dopaminergic neurons collected in control intact mice. We have found essentially similar electrophysiological criteria (frequency -1 to 10 Hz-; typical waveform of biphasic action potential - large duration above 2 ms-; inflection on the positive phase) of described firing patterns (burst and irregular ones) in grafted-DA-hiPSCs and native-DA neurons. The dorsal striatum is the main target structure of DA nigral pathway. In lack of DA release, dorsolateral striatal medium spiny neuron (MSNs) activities are imbalanced. Additional experiments are underway to assess recovery of MSNs in grafted mice. For this purpose, we will combine electrophysiological recordings of MSN activities and optogenetics to manipulate grafted-DA neuron (expressing photosensible ArchT channels) spontaneous activity. The results of these experiments will provide valuable insights regarding the neuroanatomical and functional integration of grafted neurons.
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Dates et versions

hal-04517426 , version 1 (22-03-2024)

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  • HAL Id : hal-04517426 , version 1

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Bérangère Ballion, Sébastien Brot, Laure Belnoue, Afsaneh Gaillard. Functional integration of intranigral grafted hiPSC derived dopamine neurons in a mouse model of Parkinson disease. FENS Forum 2022, Jul 2022, Paris, France. . ⟨hal-04517426⟩

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