Chemogenetic approaches reveal dual functions of microglia in seizures.

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 a

SUBMITTER: Dheer A 

PROVIDER: S-EPMC10841657 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature