A Single Hypoxic Event Ameliorates Pilocarpine Induced Hyperkinetic Movements in Planaria

Abstract

Intermittent hypoxia or hypoxia therapy is exposing an individual to oxygenation conditions that are below atmospheric levels in a planned or acute timeframe. Hypoxia therapy is a potentially novel therapeutic strategy for a variety of pathologies including: mitochondrial disorders, exercise training, and mild cognitive impairments. Mitochondrial dysfunction, hyperkinetic movements, and cognitive impairments are hallmarks of seizures and status epilepticus (SE). A seizure can be considered uncontrolled electrical activity in the brain and SE is a seizure lasting more than 30 minutes, or multiple seizures without regaining consciousness in between. We examined the possibility of using the Pilocarpine model for seizure like activity on brown planaria ( Dugesia tigrine ) . Pilocarpine is a muscarinic acetylcholine receptor agonist capable of creating seizure related brain damage. We utilized 5 mM dosages of pilocarpine and then measured open field behaviour for 3 minutes. Mobility and aversive hyperkinetic movements were observed throughout the measurement phase. After exposure to 5 mM pilocarpine, the planaria displayed behaviours consistent with seizures (e.g. aversive hyperkinetic movements and decreased mobility). Additionally, we measured the effects of an acute hypoxic event on Planaria behaviour. We used 25% carbonated water to create a hypoxic environment for the planaria and then measured mobility and hyperkinetic movements for 3 minutes. We noted that exposure to the hypoxic en-vironment produced no changes in behaviour. However, the aversive hyperkinetic move-ments produced with pilocarpine administration were completely absent when a brief (3 minutes) hypoxic episode followed the pilocarpine exposure (p < 0.05). Aversive behav-iours remained present when the ordering of pilocarpine and hypoxia were counterbal-anced. This ordering effect was consistent across 40 trials. Further evaluation of the pilo-carpine seizure model and intermittent hypoxia on planarian behaviour is warranted.