Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy

Ciric, Jelena; Lazic, Katarina; Petrović, Jelena; Kalauzi, Aleksandar; Saponjic, Jasna

doi:10.15761/tbr.1000111

Cited by 5 publications

(14 citation statements)

References 65 publications

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“…Moreover, the hallmarks of an earlier aging onset during the impaired thalamo-cortical cholinergic innervation in rat were consistently expressed through the increased EEG sigma amplitude during REM sleep, as a unique REM sleep phenomenon, alongside the broadly altered motor cortical drive to the dorsal nuchal muscles during NREM and REM sleep [9,10].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Sleep disorder and altered locomotor activity as biomarkers of the Parkinson’s disease cholinopathy in rat

Ciric

Lazic

Kapor

et al. 2018

Behavioural Brain Research

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In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Sleep disorder and altered locomotor activity as biomarkers of the Parkinson’s disease cholinopathy in rat

Ciric

Lazic

Kapor

et al. 2018

Behavioural Brain Research

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“…In addition, the altered SS dynamic has been documented in coma, epilepsy, stroke, and several forms of mental diseases (Sullivan et al, 2014), while the HVS are associated with memory impairment and the progression of brain dysfunction (Radek et al, 1994; Sales-Carbonell et al, 2013). In the rat model of PD cholinopathy, during REM sleep, the altered SS dynamic in the MCx and HVS dynamic in the MCx and hippocampus reflected the thalamo-cortical dysregulation (Ciric et al, 2017, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Although in most reviews of PD, it is stated that the motor signs first appear when about 50% of the substantia nigra (SN) dopaminergic neurons are lost, there is a good consistency in the available data which suggest that the motor signs appear when there is about a 30% loss of the total SN neurons in comparison to age-matched controls, or when about 80% of the striatal or putaminal dopamine (DA) is lost (Cheng et al, 2010). Beside the well-known reductions in dopaminergic pathways, there is also evidence for alterations in the pedunculopontine tegmental nucleus (PPT) cholinergic pathways in PD, which are associated with impaired cognition, frequent falling, gait problems and sleep disorders (Bohnen and Albin, 2011; Bohnen et al, 2012; Müller et al, 2013; Petrovic et al, 2013a,b, 2014; Ciric et al, 2016, 2017, 2018). Furthermore, there is evidence that PD is preceded by REM sleep behavioral disorders (RBD) prior to the dopaminergic neuropathology, and that these REM sleep alterations are associated with the neuronal loss of the REM sleep regulatory neuronal population, such as the sublaterodorsal nucleus (Garcia-Lorenzo et al, 2013; Boucetta et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, abnormally synchronized oscillatory activity in the cortical-basal ganglia loop is associated with motor deficit in PD (Quiroga-Varela et al, 2013; Yang et al, 2015), such as an abnormal beta synchronization (14–30 Hz) and high voltage sleep spindle (HVS) (5–13 Hz) (Buzsaki and Silva, 2012; Dejean et al, 2012). In addition there is evidence that the lack of regulation of thalamo-cortical circuits is associated with an altered SS and HVS dynamics during REM sleep (Ciric et al, 2017, 2018). Since the SS and HVS result from the interactions of the thalamic reticular, thalamo-cortical, hippocampal and cortical neurons (Buzsaki et al, 1990; Steriade, 2006; Piantoni et al, 2016), their characteristics may reflect the integrity of these circuits or serve as the biomarkers of their failing regulation in pathological condition (Warby et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat

et al. 2019

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Our previous studies in the rat model of Parkinson’s disease (PD) cholinopathy demonstrated the sleep-related alterations in electroencephalographic (EEG) oscillations at the cortical and hippocampal levels, cortical drives, and sleep spindles (SSs) as the earliest functional biomarkers preceding hypokinesia. Our aim in this study was to follow the impact of a unilateral substantia nigra pars compacta (SNpc) lesion in rat on the cortical and hippocampal sleep architectures and their EEG microstructures, as well as the cortico-hippocampal synchronizations of EEG oscillations, and the SS and high voltage sleep spindle (HVS) dynamics during NREM and REM sleep. We performed unilateral SNpc lesions using two different concentrations/volumes of 6-hydroxydopamine (6-OHDA; 12 μg/1 μl or 12 μg/2 μl). Whereas the unilateral dopaminergic neuronal loss >50% throughout the overall SNpc rostro-caudal dimension prolonged the Wake state, with no change in the NREM or REM duration, there was a long-lasting theta amplitude augmentation across all sleep states in the motor cortex (MCx), but also in the CA1 hippocampus (Hipp) during both Wake and REM sleep. We demonstrate that SS are the hallmarks of NREM sleep, but that they also occur during REM sleep in the MCx and Hipp of the control rats. Whereas SS are always longer in REM vs. NREM sleep in both structures, they are consistently slower in the Hipp. The dopaminergic neuronal loss increased the density of SS in both structures and shortened them in the MCx during NREM sleep, without changing the intrinsic frequency. Conversely, HVS are the hallmarks of REM sleep in the control rats, slower in the Hipp vs. MCx, and the dopaminergic neuronal loss increased their density in the MCx, but shortened them more consistently in the Hipp during REM sleep. In addition, there was an altered synchronization of the EEG oscillations between the MCx and Hipp in different sleep states, particularly the theta and sigma coherences during REM sleep. We provide novel evidence for the importance of the SNpc dopaminergic innervation in sleep regulation, theta rhythm generation, and SS/HVS dynamics control. We suggest the importance of the underlying REM sleep regulatory substrate to HVS generation and duration and to the cortico-hippocampal synchronizations of EEG oscillations in hemiparkinsonian rats.

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“…The first step for automatic SS and HVS detection during the 1 hr of NREM or REM sleep for each rat and experimental group was to filter the EEG signals using the 11-17 Hz band pass filter for SS, or the 4.1-10 Hz band pass filter for HVS. Then, we applied the continuous wavelet transform with the mother wavelet "cmorl-2'' MATLAB R2011a function, providing a complex Morlet wavelet with a determined central frequency f 0 = 2 (Adamczyk, Genzel, Dresler, Steiger, & Friess, 2015;Ciric et al, 2017Ciric et al, , 2018. In addition, all the SS had a minimal duration of 0.5 s, whereas all the HVS had a minimal duration of 1 s. However, because we automatically detected many false positive or negative SS or HVS, we had to visually cor- All the statistical analysis was conducted using the Mann-Whitney U-test.…”

Section: Sleep Recording and Data Analysismentioning

confidence: 99%

Sleep spindle dynamics during NREM and REM sleep following distinct general anaesthesia in control rats and in a rat model of Parkinson’s disease cholinopathy

Lazic

Ciric

Saponjic

2018

Journal of Sleep Research

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On the basis of our previous studies and the important role of the thalamo-cortical network in states of unconsciousness, such as anaesthesia and sleep, and in sleep spindles generation, we investigated sleep spindles (SS) and high-voltage sleep spindle (HVS) dynamics during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep following different types of general anaesthesia in both physiological controls and in a rat model of Parkinson's disease (PD) cholinopathy, to follow the impact of anaesthesia on post-anaesthesia sleep at the thalamo-cortical level through an altered sleep spindle dynamics. We recorded 6 hr of spontaneous sleep in all rats, both before and 48 hr after ketamine/diazepam or pentobarbital anaesthesia, and we used 1 hr of NREM or REM sleep from each to validate visually the automatically detected SS or HVS for their extraction and analysis. In the controls, SS occurred mainly during NREM, whereas HVS occurred only during REM sleep. Ketamine/diazepam anaesthesia promoted HVS, prolonged SS during NREM, induced HVS of increased frequency during REM, and increased SS/HVS densities during REM versus NREM sleep. Pentobarbital anaesthesia decreased the frequency of SS during NREM and the HVS density during REM sleep. Although the pedunculopontine tegmental nucleus lesion prolonged SS only during NREM sleep, in these rats, ketamine/diazepam anaesthesia suppressed HVS during both sleep states, whereas pentobarbital anaesthesia promoted HVS during REM sleep. The different impacts of two anaesthetic regimens on the thalamo-cortical regulatory network are expressed through their distinct sleep spindle generation and dynamics that are dependent on the NREM and REM state regulatory neuronal substrate.

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Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy

Cited by 5 publications

References 65 publications

Sleep disorder and altered locomotor activity as biomarkers of the Parkinson’s disease cholinopathy in rat

Sleep disorder and altered locomotor activity as biomarkers of the Parkinson’s disease cholinopathy in rat

Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat

Sleep spindle dynamics during NREM and REM sleep following distinct general anaesthesia in control rats and in a rat model of Parkinson’s disease cholinopathy

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