Abstract
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.
Original language | English (US) |
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Pages (from-to) | 406-418 |
Number of pages | 13 |
Journal | Brain, Behavior, and Immunity |
Volume | 115 |
DOIs | |
State | Published - Jan 2024 |
Keywords
- Chemogenetics
- Gi-Dreadds
- Hippocampus
- Kainic acid
- Microglia
- Seizures
ASJC Scopus subject areas
- Immunology
- Endocrine and Autonomic Systems
- Behavioral Neuroscience