Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein
Cellular prion protein (PrPC) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrPC protects th...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723001349 |
| _version_ | 1797812083442581504 |
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| author | Simote T. Foliaki Aleksandar Wood Katie Williams Anna Smith Ryan O. Walters Chase Baune Bradley R. Groveman Cathryn L. Haigh |
| author_facet | Simote T. Foliaki Aleksandar Wood Katie Williams Anna Smith Ryan O. Walters Chase Baune Bradley R. Groveman Cathryn L. Haigh |
| author_sort | Simote T. Foliaki |
| collection | DOAJ |
| description | Cellular prion protein (PrPC) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrPC protects the neuronal cytoskeleton, and its role in network communication, from oxidative stress damage. Oxidative stress was induced extrinsically by potassium superoxide (KO2) or intrinsically by Mito-Paraquat (MtPQ), targeting the mitochondria. In mouse neural lineage cells, KO2 was damaging to the cytoskeleton, with cells lacking PrPC (PrP-/-) damaged more than wild-type (WT) cells. In hippocampal slices, KO2 acutely inhibited neuronal communication in WT controls without damaging the cytoskeleton. This inhibition was not observed in PrP-/- slices. Neuronal communication and the cytoskeleton of PrP-/- slices became progressively disrupted and degenerated post-recovery, whereas the dysfunction in WT slices recovered in 5 days. This suggests that the acute inhibition of neuronal activity in WT slices in response to KO2 was a neuroprotective role of PrPC, which PrP-/- slices lacked. Heterozygous expression of PrPC was sufficient for this neuroprotection. Further, hippocampal slices from mice expressing PrPC without its GPI anchor (PrPGPI-/-) displayed acute inhibition of neuronal activity by KO2. However, they failed to restore normal activity and cytoskeletal formation post-recovery. This suggests that PrPC facilitates the depressive response to KO2 and its GPI anchoring is required to restore KO2-induced damages. Immuno spin-trapping showed increased radicals formed on the filamentous actin of PrP-/- and PrPGPI-/- slices, but not WT and PrP+/- slices, post-recovery suggesting ongoing dysregulation of redox balance in the slices lacking GPI-anchored PrPC. The MtPQ treatment of hippocampal slices temporarily inhibited neuronal communication independent of PrPC expression. Overall, GPI-anchored PrPC alters synapses and neurotransmission to protect and repair the neuronal cytoskeleton, and neuronal communication, from extrinsically induced oxidative stress damages. |
| first_indexed | 2024-03-13T07:32:20Z |
| format | Article |
| id | doaj.art-434f51e1d13442429fb7e4e62f8c8170 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-03-13T07:32:20Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-434f51e1d13442429fb7e4e62f8c81702023-06-04T04:23:47ZengElsevierRedox Biology2213-23172023-07-0163102733Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion proteinSimote T. Foliaki0Aleksandar Wood1Katie Williams2Anna Smith3Ryan O. Walters4Chase Baune5Bradley R. Groveman6Cathryn L. Haigh7Corresponding author.; Laboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USALaboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USALaboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USALaboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USALaboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USALaboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USALaboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USACorresponding author.; Laboratory of Persistent Viral Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, MT, 59840, USACellular prion protein (PrPC) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrPC protects the neuronal cytoskeleton, and its role in network communication, from oxidative stress damage. Oxidative stress was induced extrinsically by potassium superoxide (KO2) or intrinsically by Mito-Paraquat (MtPQ), targeting the mitochondria. In mouse neural lineage cells, KO2 was damaging to the cytoskeleton, with cells lacking PrPC (PrP-/-) damaged more than wild-type (WT) cells. In hippocampal slices, KO2 acutely inhibited neuronal communication in WT controls without damaging the cytoskeleton. This inhibition was not observed in PrP-/- slices. Neuronal communication and the cytoskeleton of PrP-/- slices became progressively disrupted and degenerated post-recovery, whereas the dysfunction in WT slices recovered in 5 days. This suggests that the acute inhibition of neuronal activity in WT slices in response to KO2 was a neuroprotective role of PrPC, which PrP-/- slices lacked. Heterozygous expression of PrPC was sufficient for this neuroprotection. Further, hippocampal slices from mice expressing PrPC without its GPI anchor (PrPGPI-/-) displayed acute inhibition of neuronal activity by KO2. However, they failed to restore normal activity and cytoskeletal formation post-recovery. This suggests that PrPC facilitates the depressive response to KO2 and its GPI anchoring is required to restore KO2-induced damages. Immuno spin-trapping showed increased radicals formed on the filamentous actin of PrP-/- and PrPGPI-/- slices, but not WT and PrP+/- slices, post-recovery suggesting ongoing dysregulation of redox balance in the slices lacking GPI-anchored PrPC. The MtPQ treatment of hippocampal slices temporarily inhibited neuronal communication independent of PrPC expression. Overall, GPI-anchored PrPC alters synapses and neurotransmission to protect and repair the neuronal cytoskeleton, and neuronal communication, from extrinsically induced oxidative stress damages.http://www.sciencedirect.com/science/article/pii/S2213231723001349Oxidative stressPrPPrion diseasePrion proteinNeuronal cytoskeletonHippocampal CA1 long-term potentiation |
| spellingShingle | Simote T. Foliaki Aleksandar Wood Katie Williams Anna Smith Ryan O. Walters Chase Baune Bradley R. Groveman Cathryn L. Haigh Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein Redox Biology Oxidative stress PrP Prion disease Prion protein Neuronal cytoskeleton Hippocampal CA1 long-term potentiation |
| title | Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein |
| title_full | Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein |
| title_fullStr | Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein |
| title_full_unstemmed | Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein |
| title_short | Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein |
| title_sort | temporary alteration of neuronal network communication is a protective response to redox imbalance that requires gpi anchored prion protein |
| topic | Oxidative stress PrP Prion disease Prion protein Neuronal cytoskeleton Hippocampal CA1 long-term potentiation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723001349 |
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