Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.

Abstract

We investigated the prodromal alterations of local sleep, particularly the motor cortical and hippocampal sleep, along with spontaneous locomotor activity in the rat models of Parkinson's disease (PD). We performed our experiments in adult, male Wistar rats, chronically implanted for sleep recording and divided into four experimental groups: the control (implanted controls), the bilateral pedunculopontine tegmental nucleus (PPT) lesions (PD cholinopathy), the unilateral substantia nigra pars compacta (SNpc) lesions (hemiparkinsonism) and the unilateral SNpc/bilateral PPT lesions (hemiparkinsonism with PD cholinopathy). We followed their sleep, basal locomotor activity and spatial habituation for 14 days following the surgical procedures. Severe prodromal local sleep disturbances in the hemiparkinsonian rats were expressed as sleep fragmentation and distinct local NREM/REM EEG microstructure alterations in both the motor cortex and the hippocampus. Alongside the state-unrelated role of the dopaminergic control of theta oscillations and NREM/REM related sigma and beta oscillations, we demonstrated that the REM neurochemical regulatory substrate is particularly important in the dopaminergic control of beta oscillations. In addition, hippocampal prodromal sleep disorders in the hemiparkinsonian rats were expressed as NREM/REM fragmentation and the opposite impact of dopaminergic versus cholinergic control of the NREM delta and beta oscillation amplitudes in the hippocampus, likewise in the motor cortex versus the hippocampus. All these distinct prodromal local sleep disorders and the dopaminergic vs. cholinergic impact on NREM/REM EEG microstructure alterations are of fundamental importance for the further development and follow-up of PD-modifying therapies, and for the identification of patients who are at risk of developing PD.