Microglia Modulate the Breathing Phenotype in Chronic Epilepsy

Microglia Modulate the Breathing Phenotype in Chronic Epilepsy

Life Sciences

Bíborka Balázs

2023

Epilepsy is one of the most common neurodegenerative diseases, characterised by electrical imbalances in neurons yielding seizure activity. Around 600 people with epilepsy in the UK die every year from sudden unexpected death in epilepsy (SUDEP). A major cause of SUDEP, seizure-induced cardiorespiratory autonomic dysfunction, is known, however exact neuronal and microglial inflammatory mechanisms governing this impairment have not been characterised. Microglia, the resident multifunctional immune cells of the central nervous system were shown to surround cardiorespiratory neurons and to exhibit both pro- and anti-epileptic functions, supporting their modulatory role in the breathing phenotype characteristic of epilepsy. Cardiorespiratory dysfunction was previously suggested to arise resulting from propagating neuronal hyperexcitability into the brainstem and the consequent microglia-induced neuroinflammation. Based on this phenotype we hypothesize that seizure-induced microglial activation changes from being initially beneficial against seizures in acute epilepsy, to detrimental by progressively decreasing the threshold for seizures in chronic epilepsy, to ultimately fatal by compromising the activity of cardiorespiratory autonomic neurons in the brainstem. Cardiorespiratory function was examined in awake, freely moving epileptic and sham-treated mice in response to different levels of CO2 levels. Microglia activity rescued the breathing phenotype in acute but worsened it in chronic epilepsy. These findings suggest microglia may remodel cardiorespiratory neuronal circuits in epilepsy potentially leading to SUDEP. This research suggests directions for novel treatments for epilepsy that appropriately modify microglia activity.