Chemogenetic approaches reveal dual functions of microglia in seizures
Copyright © 2023 Elsevier Inc. All rights reserved..
Microglia are key players in maintaining brain homeostasis and exhibit phenotypic alterations in response to epileptic stimuli. However, it is still relatively unknown if these alterations are pro- or anti-epileptic. To unravel this dilemma, we employed chemogenetic manipulation of microglia using the artificial Gi-Dreadd receptor within a kainic acid (KA) induced murine seizure model. Our results indicate that acute Gi-Dreadd activation with Clozapine-N-Oxide can reduce seizure severity. Additionally, we observed increased interaction between microglia and neuronal soma, which correlated with reduced neuronal hyperactivity. Interestingly, prolonged activation of microglial Gi-Dreadds by repeated doses of CNO over 3 days, arrested microglia in a less active, homeostatic-like state, which associated with increased neuronal loss after KA induced seizures. RNAseq analysis revealed that prolonged activation of Gi-Dreadd interferes with interferon β signaling and microglia proliferation. Thus, our findings highlight the importance of microglial Gi signaling not only during status epilepticus (SE) but also within later seizure induced pathology.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Brain, behavior, and immunity - 115(2024) vom: 20. Jan., Seite 406-418 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dheer, Aastha [VerfasserIn] |
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| Links: |
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| Themen: |
Anticonvulsants |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2023.11.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364179783 |
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| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a Microglia are key players in maintaining brain homeostasis and exhibit phenotypic alterations in response to epileptic stimuli. However, it is still relatively unknown if these alterations are pro- or anti-epileptic. To unravel this dilemma, we employed chemogenetic manipulation of microglia using the artificial Gi-Dreadd receptor within a kainic acid (KA) induced murine seizure model. Our results indicate that acute Gi-Dreadd activation with Clozapine-N-Oxide can reduce seizure severity. Additionally, we observed increased interaction between microglia and neuronal soma, which correlated with reduced neuronal hyperactivity. Interestingly, prolonged activation of microglial Gi-Dreadds by repeated doses of CNO over 3 days, arrested microglia in a less active, homeostatic-like state, which associated with increased neuronal loss after KA induced seizures. RNAseq analysis revealed that prolonged activation of Gi-Dreadd interferes with interferon β signaling and microglia proliferation. Thus, our findings highlight the importance of microglial Gi signaling not only during status epilepticus (SE) but also within later seizure induced pathology | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Chemogenetics | |
| 650 | 4 | |a Gi-Dreadds | |
| 650 | 4 | |a Hippocampus | |
| 650 | 4 | |a Kainic acid | |
| 650 | 4 | |a Microglia | |
| 650 | 4 | |a Seizures | |
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| 700 | 1 | |a Zheng, Jiaying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lingxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Shunyi |e verfasserin |4 aut | |
| 700 | 1 | |a Haruwaka, Koichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Min-Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Barath, Abhijeet |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Dai-Shi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Long-Jun |e verfasserin |4 aut | |
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