Network dysfunction in α-synuclein transgenic mice and human Lewy body dementia

摘要: Author(s): Morris, Meaghan; Sanchez, Pascal E; Verret, Laure; Beagle, Alexander J; Guo, Weikun; Dubal, Dena; Ranasinghe, Kamalini G; Koyama, Akihiko; Ho, Kaitlyn; Yu, Gui-Qiu; Vossel, Keith A; Mucke, Lennart | Abstract: ObjectiveDementia with Lewy bodies (DLB) is associated the accumulation of wild-type human α-synuclein (SYN) in neurons and prominent slowing brain oscillations on electroencephalography (EEG). However, it remains uncertain whether EEG abnormalities are actually caused by SYN.MethodsTo determine SYN can cause neural network abnormalities, we performed recordings analyzed expression neuronal activity-dependent gene products transgenic mice. We also carried out comparative analyses humans DLB.ResultsWe demonstrate that mice causes a left shift spectral power closely resembles observed DLB patients. Surprisingly, had seizures showed molecular hippocampal alterations indicative aberrant excitability, including calbindin depletion dentate gyrus. In postmortem tissues from patients, found reduced levels mRNA Furthermore, nearly one quarter patients myoclonus, clinical sign excitability was an earlier age onset cognitive impairments. mice, partial suppression epileptiform activity did not alter their power. amyloid precursor protein power.InterpretationWe conclude slows and, parallel, escalate into seizure activity. The potential role merits further investigation.