Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts
Summary: Neuronal swelling during cytotoxic edema is triggered by Na+ and Cl− entry and is Ca2+ independent. However, the causes of neuronal death during swelling are unknown. Here, we investigate the role of large-conductance Pannexin-1 (Panx1) channels in neuronal death during cytotoxic edema. Pan...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723011403 |
| _version_ | 1827808390563233792 |
|---|---|
| author | Nicholas L. Weilinger Kai Yang Hyun B. Choi Christopher J. Groten Stefan Wendt Madhuvika Murugan Leigh E. Wicki-Stordeur Louis-Philippe Bernier Prashanth S. Velayudhan Jiaying Zheng Jeffrey M. LeDue Ravi L. Rungta John R. Tyson Terrance P. Snutch Long-Jun Wu Brian A. MacVicar |
| author_facet | Nicholas L. Weilinger Kai Yang Hyun B. Choi Christopher J. Groten Stefan Wendt Madhuvika Murugan Leigh E. Wicki-Stordeur Louis-Philippe Bernier Prashanth S. Velayudhan Jiaying Zheng Jeffrey M. LeDue Ravi L. Rungta John R. Tyson Terrance P. Snutch Long-Jun Wu Brian A. MacVicar |
| author_sort | Nicholas L. Weilinger |
| collection | DOAJ |
| description | Summary: Neuronal swelling during cytotoxic edema is triggered by Na+ and Cl− entry and is Ca2+ independent. However, the causes of neuronal death during swelling are unknown. Here, we investigate the role of large-conductance Pannexin-1 (Panx1) channels in neuronal death during cytotoxic edema. Panx1 channel inhibitors reduce and delay neuronal death in swelling triggered by voltage-gated Na+ entry with veratridine. Neuronal swelling causes downstream production of reactive oxygen species (ROS) that opens Panx1 channels. We confirm that ROS activates Panx1 currents with whole-cell electrophysiology and find scavenging ROS is neuroprotective. Panx1 opening and subsequent ATP release attract microglial processes to contact swelling neurons. Depleting microglia using the CSF1 receptor antagonist PLX3397 or blocking P2Y12 receptors exacerbates neuronal death, suggesting that the Panx1-ATP-dependent microglia contacts are neuroprotective. We conclude that cytotoxic edema triggers oxidative stress in neurons that opens Panx1 to trigger death but also initiates neuroprotective feedback mediated by microglia contacts. |
| first_indexed | 2024-03-11T22:26:30Z |
| format | Article |
| id | doaj.art-15c0151341174dd0a284baf30f872a0d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T22:26:30Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-15c0151341174dd0a284baf30f872a0d2023-09-24T05:15:02ZengElsevierCell Reports2211-12472023-10-014210113128Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contactsNicholas L. Weilinger0Kai Yang1Hyun B. Choi2Christopher J. Groten3Stefan Wendt4Madhuvika Murugan5Leigh E. Wicki-Stordeur6Louis-Philippe Bernier7Prashanth S. Velayudhan8Jiaying Zheng9Jeffrey M. LeDue10Ravi L. Rungta11John R. Tyson12Terrance P. Snutch13Long-Jun Wu14Brian A. MacVicar15Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Corresponding authorDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Stomatology and Department of Neuroscience, Université de Montréal, Montréal, QC, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Corresponding authorSummary: Neuronal swelling during cytotoxic edema is triggered by Na+ and Cl− entry and is Ca2+ independent. However, the causes of neuronal death during swelling are unknown. Here, we investigate the role of large-conductance Pannexin-1 (Panx1) channels in neuronal death during cytotoxic edema. Panx1 channel inhibitors reduce and delay neuronal death in swelling triggered by voltage-gated Na+ entry with veratridine. Neuronal swelling causes downstream production of reactive oxygen species (ROS) that opens Panx1 channels. We confirm that ROS activates Panx1 currents with whole-cell electrophysiology and find scavenging ROS is neuroprotective. Panx1 opening and subsequent ATP release attract microglial processes to contact swelling neurons. Depleting microglia using the CSF1 receptor antagonist PLX3397 or blocking P2Y12 receptors exacerbates neuronal death, suggesting that the Panx1-ATP-dependent microglia contacts are neuroprotective. We conclude that cytotoxic edema triggers oxidative stress in neurons that opens Panx1 to trigger death but also initiates neuroprotective feedback mediated by microglia contacts.http://www.sciencedirect.com/science/article/pii/S2211124723011403CP: NeuroscienceCP: Molecular biology |
| spellingShingle | Nicholas L. Weilinger Kai Yang Hyun B. Choi Christopher J. Groten Stefan Wendt Madhuvika Murugan Leigh E. Wicki-Stordeur Louis-Philippe Bernier Prashanth S. Velayudhan Jiaying Zheng Jeffrey M. LeDue Ravi L. Rungta John R. Tyson Terrance P. Snutch Long-Jun Wu Brian A. MacVicar Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts Cell Reports CP: Neuroscience CP: Molecular biology |
| title | Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts |
| title_full | Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts |
| title_fullStr | Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts |
| title_full_unstemmed | Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts |
| title_short | Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts |
| title_sort | pannexin 1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts |
| topic | CP: Neuroscience CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723011403 |
| work_keys_str_mv | AT nicholaslweilinger pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT kaiyang pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT hyunbchoi pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT christopherjgroten pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT stefanwendt pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT madhuvikamurugan pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT leighewickistordeur pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT louisphilippebernier pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT prashanthsvelayudhan pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT jiayingzheng pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT jeffreymledue pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT ravilrungta pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT johnrtyson pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT terrancepsnutch pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT longjunwu pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts AT brianamacvicar pannexin1openinginneuronaledemacausescelldeathbutalsoleadstoprotectionviaincreasedmicrogliacontacts |