Abstract
In several tauopathies such as Alzheimer's disease (AD), an increased incidence of seizures is observed. Tau, one of the major proteins implicated in AD pathology, is an important regulator of neural network excitability and might participate in the underlying epileptic cascade. However, the mechanisms underlying this relationship are not fully elucidated. We aim to investigate this mechanism by analyzing seizure susceptibility to the convulsant pentylenetetrazole (PTZ) in a novel rodent tauopathy model. A single dose of PTZ was systemically injected in Tau58/4 transgenic mice. To investigate whether young and aged heterozygous (HET) mice exhibit a higher susceptibility to seizures in comparison with wild-type (WT) littermates, video electroencephalography (EEG) in combination with behavioral scoring according to a modified Racine scale was used. The employment of different dosage groups enabled us to characterize the dose range reliably inducing seizures. Here, we report an increased seizure susceptibility in young but not in old HET Tau58/4 mice. Young HET animals displayed more severe seizures and had a reduced latency to the first seizure compared to WTs. Also, age-related differences in susceptibility could be demonstrated for both genotypes. Identification and targeting of secondary diseases such as epilepsy, which aggravate dementia and lead to earlier institutionalization, is key. This study finds that tau pathology itself is sufficient to alter seizure susceptibility in a rodent model, indicating that the disease process is crucial in the emergence of epilepsy in patients with tauopathy.