Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1
We recently described new pathogenic variants in VRK1, in patients affected with distal Hereditary Motor Neuropathy associated with upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Motor Neurons (hiPSC-MN) from these patients display Cajal Bodies (CBs) disassembly an...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996121003582 |
| _version_ | 1798025255130759168 |
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| author | Rémi Bos Khalil Rihan Patrice Quintana Lara El-Bazzal Nathalie Bernard-Marissal Nathalie Da Silva Rosette Jabbour André Mégarbané Marc Bartoli Frédéric Brocard Valérie Delague |
| author_facet | Rémi Bos Khalil Rihan Patrice Quintana Lara El-Bazzal Nathalie Bernard-Marissal Nathalie Da Silva Rosette Jabbour André Mégarbané Marc Bartoli Frédéric Brocard Valérie Delague |
| author_sort | Rémi Bos |
| collection | DOAJ |
| description | We recently described new pathogenic variants in VRK1, in patients affected with distal Hereditary Motor Neuropathy associated with upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Motor Neurons (hiPSC-MN) from these patients display Cajal Bodies (CBs) disassembly and defects in neurite outgrowth and branching. We here focused on the Axonal Initial Segment (AIS) and the related firing properties of hiPSC-MNs from these patients. We found that the patient's Action Potential (AP) was smaller in amplitude, larger in duration, and displayed a more depolarized threshold while the firing patterns were not altered. These alterations were accompanied by a decrease in the AIS length measured in patients' hiPSC-MNs. These data indicate that mutations in VRK1 impact the AP waveform and the AIS organization in MNs and may ultimately lead to the related motor neuron disease. |
| first_indexed | 2024-04-11T18:15:47Z |
| format | Article |
| id | doaj.art-e0889f703ae042e3a01c7a9e37be8b23 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T18:15:47Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-e0889f703ae042e3a01c7a9e37be8b232022-12-22T04:09:55ZengElsevierNeurobiology of Disease1095-953X2022-03-01164105609Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1Rémi Bos0Khalil Rihan1Patrice Quintana2Lara El-Bazzal3Nathalie Bernard-Marissal4Nathalie Da Silva5Rosette Jabbour6André Mégarbané7Marc Bartoli8Frédéric Brocard9Valérie Delague10Aix Marseille Univ, CNRS, Institut de Neurosciences de la Timone (INT), UMR 7289, Marseille, France; Corresponding author at: Institut de Neurosciences de la Timone, Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université, UMR 7289, 27 bd Jean Moulin, 13385 Marseille cedex 05, France.Aix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, FranceAix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, FranceAix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, FranceAix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, FranceAix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, FranceNeurology Division, Department of Internal Medicine, St George Hospital University Medical Center, University of Balamand, Beirut, LebanonDepartment of Human Genetics, Gilbert and RoseMary Chagoury Hospital, Lebanese American University, Byblos, LebanonAix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, FranceAix Marseille Univ, CNRS, Institut de Neurosciences de la Timone (INT), UMR 7289, Marseille, FranceAix Marseille Univ, Inserm, MMG, U 1251, Institut Marseille Maladies Rares (MarMaRa), Marseille, France; Corresponding author at: Inserm U 1251, Marseille Medical Genetics, Faculté de Médecine de la Timone, Aix Marseille Université, 27 bd Jean Moulin, 13385 Marseille cedex 05, France.We recently described new pathogenic variants in VRK1, in patients affected with distal Hereditary Motor Neuropathy associated with upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Motor Neurons (hiPSC-MN) from these patients display Cajal Bodies (CBs) disassembly and defects in neurite outgrowth and branching. We here focused on the Axonal Initial Segment (AIS) and the related firing properties of hiPSC-MNs from these patients. We found that the patient's Action Potential (AP) was smaller in amplitude, larger in duration, and displayed a more depolarized threshold while the firing patterns were not altered. These alterations were accompanied by a decrease in the AIS length measured in patients' hiPSC-MNs. These data indicate that mutations in VRK1 impact the AP waveform and the AIS organization in MNs and may ultimately lead to the related motor neuron disease.http://www.sciencedirect.com/science/article/pii/S0969996121003582MotoneuronAction potential waveformVRK1hiPSCInherited peripheral neuropathyMotor neuron disease |
| spellingShingle | Rémi Bos Khalil Rihan Patrice Quintana Lara El-Bazzal Nathalie Bernard-Marissal Nathalie Da Silva Rosette Jabbour André Mégarbané Marc Bartoli Frédéric Brocard Valérie Delague Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 Neurobiology of Disease Motoneuron Action potential waveform VRK1 hiPSC Inherited peripheral neuropathy Motor neuron disease |
| title | Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 |
| title_full | Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 |
| title_fullStr | Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 |
| title_full_unstemmed | Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 |
| title_short | Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1 |
| title_sort | altered action potential waveform and shorter axonal initial segment in hipsc derived motor neurons with mutations in vrk1 |
| topic | Motoneuron Action potential waveform VRK1 hiPSC Inherited peripheral neuropathy Motor neuron disease |
| url | http://www.sciencedirect.com/science/article/pii/S0969996121003582 |
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