Alterations in non-REM sleep and EEG spectra precede REM-sleep deficits in a model of synucleinopathy

Background: Sleep disturbances often precede motor symptoms in neurodegenerative diseases like Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Neuroinflammation is implicated in PD pathophysiology and may contribute to non-motor symptoms such as sleep disturbances. The Thy1-αSyn mouse model, overexpressing human alpha-synuclein (αSyn), mimics key aspects of PD and DLB, making it valuable for studying related sleep disturbances and neuroinflammatory changes.

Objective: To investigate early-stage alterations in sleep architecture, electroencephalographic (EEG) patterns, and neuroinflammation in Thy1-αSyn mice.

Methods: We used telemetric EEG/electromyography (EMG) with video surveillance to compare sleep patterns and EEG spectral power between 2.5- and 4.5-month-old male Thy1-αSyn transgenic mice and wild-type littermates. Neuroinflammation was assessed by examining microglial (Iba1) and astrocytic (GFAP) activation in key sleep-regulating brain regions.

Results: Thy1-αSyn mice showed decreased resting wake time and increased non-REM sleep, with altered sleep bout frequency and length, indicating significant sleep architecture changes. Spectral analysis revealed a shift from higher to lower frequency bands, suggesting early neural circuitry disruptions due to αSyn overexpression. Significant microglial activation was observed at 3 months, with astrogliosis progressing by 5 months in key sleep-regulating regions, indicating that neuroinflammation may contribute to the observed sleep disturbances.

Conclusions: Early-stage Thy1-αSyn mice exhibit significant sleep architecture changes, EEG spectral shifts, and neuroinflammatory alterations. These findings suggest that neuroinflammation may play a role in the initial pathophysiological changes in PD and related synucleinopathies. Sleep, EEG, and neuroinflammatory changes could serve as early biomarkers for these diseases.