Neurological Disease Rises from Ocean To Bring Model for Human Epilepsy to Life

Shifting offshore winds and ocean upwellings driven by a cold water climate oscillation off the California coast have fueled a decade of harmful algal blooms that produce domoic acid (DA). These blooms can poison thousands of marine mammals within a few months. Few dolphins or other cetaceans survive on the beach long enough for observation although occasionally seizure behavior and high DA levels in urine are confirmed in dolphins. However, sea lions which often survive stranding to be clinically observed, can serve as a good surrogate to understand what may be happening in other animals restricted to the marine environment, especially the long and short-beaked dolphins (Delphinus capensis and D. delphis) commonly found stranded with sea lions. Analysis of sea lions in clinics determined nearly 1/4 have a disease similar to human temporal lobe epilepsy (TLE) and >100 were observed to develop recurrent spontaneous seizures (RSS) in captivity weeks to months after poisoning. The inference that neurological disease can emerge from DA poisoning originated from a single human case 20 yr earlier where TLE developed 1 yr after acute DA poisoning. We adapted an established laboratory rat model for TLE to verify that a single episode of DA poisoning can induce a permanent state of epileptic disease. We find that DA is highly lethal to rats but under careful exposure conditions (nonsymptomatic doses of 1.0 mg/kg DA given hourly until first sign of convulsive behavior) rats recover from status epilepticus to eventually develop RSS. Observation by 6 hr/wk video monitoring over 6 mo show 90% develop RSS and all develop aggressive behavior toward conspecifics. The latent period for 50% to reach these behaviors is 8 and 4 weeks, respectively. Rats elicited an emotional reaction to handling tests within one week that increased in aggressive intensity and occasionally convulsive seizures. Intense emotional behavior persisted for the 6 mo testing period. We conclude that a single episode of seizure behavior in response to DA induces a permanent state of RSS and aggressive behavior. These hallmark characteristics of the epileptic state also observed in the sea lion clinics are likely occurring unseen in the marine environment with a life-long impact on many of the species of dolphins, whales and sea birds thought only to be acutely poisoned by DA-producing algal blooms. These results verify DA as an environmental cause of epilepsy and define an experimental model to probe a real life scenario existing in our oceans that can be linked to a current climate oscillation.