The effects of levetiracetam on glutamatergic synaptic transmission: Crayfish and Drosophila NMJs

Abstract

Epilepsy is a neurological disorder characterized by recurring, unpredictable seizures. Its disease burden is high, seeing as it ranks fourth in the world's neurological disorders burden following: tension-type headaches, migraines, and Alzheimer's disease. The commonly used anti-epileptic drug levetiracetam (Keppra) reduces epileptic seizures, but the exact mechanism through which it works is not known. Some studies suggest sodium and/or potassium ionic channels are directly altered reducing membrane excitability, while others suggest the drug interacts with SV2 protein to alter synaptotagmin (a calcium sensor protein) action in the presynaptic nerve terminal (reducing excitability). The glutamatergic synapses at crayfish and larval Drosophila neuromuscular junctions (NMJs) were used to assess the drug's action. The evoked excitatory junction potentials (EJPs) of the crayfish NMJ were enhanced through exposure to 1 mM of the drug, but not lower doses, with 20 minutes of stimulation after 10 minutes of static incubation. However, no significant alterations were noted in the amplitude of the EJPs at the Drosophila NMJ during the 20 minutes of stimulation at 5 Hz. The crayfish model effects of levetiracetam were then used as an authentic curriculum undergraduate research experience (ACURE) in a neurophysiology teaching laboratory with 16 students. It appears levetiracetam acts differently in different animal models, or varied experimental conditions are required to note its effects.