Spontaneous Recurrent Absence Seizure-like Events in Wild-Caught Rats
| Autor: | Jon D. Reuter, Daniel S. Barth, Rebecca A. Kubiak, Toni T. Mufford, Carmen J. Booth, F. Edward Dudek, Jeremy J. Taylor |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Rodent Movement Physiology Animals Wild Neurological disorder Motor Activity Electroencephalography 03 medical and health sciences Epilepsy 0302 clinical medicine Seizures biology.animal Genetic model medicine Animals Rats Long-Evans Research Articles medicine.diagnostic_test biology General Neuroscience medicine.disease Circadian Rhythm Rats Electrophysiology Absence seizure 030104 developmental biology Ethosuximide Anticonvulsants Female Electrocorticography 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | The Journal of Neuroscience. 39:4829-4841 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1167-18.2019 |
| Popis: | Absence epilepsy is a heritable human neurological disorder characterized by brief nonconvulsive seizures with behavioral arrest, moderate-to-severe loss of consciousness (absence), and distinct spike-wave discharges (SWDs) in the EEG and electrocorticogram (ECoG). Genetic models of this disorder have been created by selectively inbreeding rats for absence seizure-like events with similar electrical and behavioral characteristics. However, these events are also common in outbred laboratory rats, raising concerns about whether SWD/immobility accurately reflects absence epilepsy as opposed to “normal” rodent behavior. We hypothesized that, if SWD/immobility models absence seizures, it would not exist in wild-caught rats due to the pressures of natural selection. To test this hypothesis, we compared chronic video/electrocorticogram recordings from male and female wild-caught (Brown-Norway [BN]) rats to recordings from laboratory outbred BN, outbred Long–Evans, and inbred WAG/Rij rats (i.e., a model of absence epilepsy). Wild-caught BN rats displayed absence-like SWD/immobility events that were highly similar to outbred BN rats in terms of spike-wave morphology, frequency, diurnal rhythmicity, associated immobility, and sensitivity to the anti-absence drug, ethosuximide; however, SWD bursts were less frequent and of shorter duration in wild-caught and outbred BN rats than the outbred Long–Evans and inbred WAG/Rij strains. We conclude that SWD/immobility in rats does not represent absence seizures, although they appear to have many similarities. In wild rats, SWD/immobility appears to represent normal brain activity that does not reduce survival in natural environments, a conclusion that logically extends to outbred laboratory rats and possibly to those that have been inbred to model absence epilepsy. SIGNIFICANCE STATEMENT Spike-wave discharges (SWDs), behavioral arrest, and diminished consciousness are cardinal signs of seizures in human absence epilepsy and are used to model this disorder in inbred rats. These characteristics, however, are routinely found in outbred laboratory rats, leading to debate on whether SWD/immobility is a valid model of absence seizures. The SWD/immobility events in wild-caught rats appear equivalent to those found in outbred and inbred rat strains, except for lower incidence and shorter durations. Our results indicate that the electrophysiological and behavioral characteristics of events underlying hypothetical absence epilepsy in rodent models are found in wild rats captured in their natural environment. Other criteria beyond observation of SWDs and associated immobility are required to objectively establish absence epilepsy in rat models. |
| Databáze: | OpenAIRE |
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