Rationale: We have found multiple novel roles for voltage-gated potassium channel auxiliary subunit DPP6 (Dipeptidyl Peptidase-Like 6) including in neuronal development, leaning and memory and connections to Alzheimer disease (AD)/dementia. Novel structures associated with amyloid-β (Aβ) were found in hippocampal area CA1 in aging DPP6-KO mice, apparently derived from degenerating presynaptic terminals, that are significantly more prevalent in DPP6-KO mice compared to WT mice. Aging DPP6-KO mice also show increased Aβ, tau pathologies, neuroinflammation and sleep disturbances. AD patients have about eight-fold risk of epileptic seizures compared to age-matched population. In this study, we examined seizure in DPP6-KO mice and littermate controls by detecting EEG spike-wave discharges, hallmarks of nonconvulsive seizure with no accompanying tonic-clonic movements.
Methods: We used
surgical implantation of the HD-X02 telemetry system (DSI), and electrophysiological data were collected for 2-5 days using Ponemah software.
Results:
Twelve-month-old DPP6-KO mice exhibited a significantly higher prevalence of spike wave discharges and nonconvulsive seizures compared to WT controls. Aging DPP6-KO mice showed significantly longer spike train durations during five days of EEG 5 recordings and increased average spike train duration. We also found an increase in the number of high amplitude single spikes (over 400 mV) in EEG recordings in 12-month-old DPP6-KO mice
. In contrast, the adult three-month-old DPP6-KO mice have no significant increases in seizures reported compared to same-aged WT littermates.
Conclusions: Together these results indicate that DPP6-KO mice show age-dependent changes in seizure and high amplitude single spikes, further supporting a role of DPP6 in Alzheimer's/dementia.
Funding: This work was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human Development.