Research Funded by the Epilepsy Foundation Sheds Light on the Role of Neurotransmitters in Sudden Unexpected Death in Epilepsy

Research by Epilepsy Foundation grantee Dr. Gordon Buchanan and colleagues sought to study role of neurotransmitters, such as serotonin (5-HT) and norepinephrine (NE), in sudden unexpected death in epilepsy (SUDEP). Their work was published in an Epilepsia article titled, “Effect of monoamine reuptake inhibition and α1 blockade on respiratory arrest and death following electroshock-induced seizures in mice.” 

Purpose

• SUDEP can be defined as sudden death in a person with epilepsy who is otherwise healthy.
• SUDEP is a leading cause of death in people with epilepsy.
• The neurotransmitter serotonin (also called 5-HT) may be involved in SUDEP, but the role of the neurotransmitter norepinephrine (NE) is still not fully understood.
  • Breathing was studied because in most witnessed cases of SUDEP the seizure is followed by a stop in breathing.

Description of Study

• All procedures were approved by regulatory bodies to ensure that animals did not experience undue pain.
• The authors induced acute seizures in mice using the maximal electroshock (MES) method.
• After seizures were simulated, levels of 5-HT and NA were artificially changed by the following techniques:
  • Genetic manipulation, such as knockout technology
  • Drugs that selectively targeted the 5-HT or the NE systems
• The effects on the incidence of death and on seizure‐induced respiratory arrest (S‐IRA) in mice were studied. 

Results

• S-IRA was prevented when levels of 5-HT and NE were increased. Hence an increase in levels of 5-HT and NE proved to be protective.
• This protective effect was not seen when NE was blocked. 
• These results suggest that 5-HT and NE are both critical for regulation of breathing following a seizure. 

What does this mean?

• The mechanisms underlying SUDEP are unfortunately not completely understood. 
• In this study, the authors used a combination of genetic and pharmacological technologies to add to existing knowledge about the role of neurotransmitters 5-HT and NE in SUDEP. 
• Although more studies are needed to prove the specific role of 5-HT and NE in SUDEP, these findings can be used to design possible therapies to prevent SUDEP.
• Another future application could be therapies that target both the 5-HT and NE systems.

References

• Kruse SW, Dayton KG, Purnell BS, Rosner JI, Buchanan GF. Effect of monoamine reuptake inhibition and α1 blockade on respiratory arrest and death following electroshock-induced seizures in mice. Epilepsia. 2019 Mar;60(3):495-507.