Early Effects of Alpha-Synuclein Depletion by Pan-Neuronal Inactivation of Encoding Gene on Electroencephalogram Coherence between Different Brain Regions in Mice

Abstract

Inactivation of the Snca gene in young mice by chronic injections of tamoxifen (TAM), a selective estrogen receptor modifier, has been shown to decrease the level of alpha-synuclein, a key peptide in the pathogenesis of Parkinson’s disease. In young mice, different time courses of the effect were observed in different brain areas, meaning associated disturbances in the intracerebral relations, namely in brain function after TAM-induced synucleinopathy. Methods: We analyzed electroencephalogram (EEG) coherence (“functional connectivity”) between the cortex (MC), putamen (Pt), and dopamine-producing brain regions (ventral tegmental area, VTA, and substantia nigra, SN) in two groups of two-month-old male mice. We compared EEG coherences in the conditional knockout Sncaflox/flox mice with those in their genetic background (C57Bl6J) one, two, and three months after chronic (for five days) intraperitoneal injections of TAM or the vehicle (corn oil). The EEG coherences in the TAM-treated group were compared with those in the alpha-synuclein knockout mice. Results: A significant suppression of EEG coherence in the TAM-treated mice versus the vehicle group was observed in all inter-structural relations, with the exception of MC-VTA at one and three months and VTA-SN at two months after the injections. Suppressive changes in EEG coherence were observed in the alpha-synuclein knockout mice as well; the changes were similar to those in TAM-treated mice three months after treatment. Conclusion: our data demonstrate a combined time-dependent suppressive effect induced by TAM on intracerebral EEG coherence.