DEVELOPMENT OF A PRECLINICAL MODEL OF REM SLEEP BEHAVIOR DISORDER (RBD), A PRODROMAL PARASOMNIA OF PARKINSON’S DISEASE, IN M83 TRANSGENIC MICE - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2023

DEVELOPMENT OF A PRECLINICAL MODEL OF REM SLEEP BEHAVIOR DISORDER (RBD), A PRODROMAL PARASOMNIA OF PARKINSON’S DISEASE, IN M83 TRANSGENIC MICE

Résumé

There is a lack of preclinical models of Parkinson’s Disease (PD) that chronologically reproduce the underlying progressive brain invasion by toxic intraneuronal aggregates rich in misfolded alpha-synuclein (a-Syn). It is of particular importance to model the pre-symptomatic period during which PD insidiously settles in the brain, long before the onset of cardinal motor symptoms. REM sleep Behavior Disorder (RBD), a parasomnia with loss of muscle atonia during REM sleep is a highly recognized prodromal PD biomarker at 10 years. Since RBD and PD seem to be chronologically linked, there is an interest in investigating RBD etiology because of its predictive nature. It might reflect dysfunction/degeneration of brainstem sublaterodorsal nucleus (SLD) as its genetic inactivation in rodents is sufficient to recapitulate human RBD. We hypothesize that a synucleinopathic attack might target SLD before spreading over years in the caudo-rostral brain axis. To test this hypothesis, we used transgenic homozygote M83 mice, a widely used PD model as expressing the human a-Syn with A53T mutation and depicting PD-like behaviors around 9-months age. M83 mice (5-months age) were prepared for polysomnographic and video recordings to assess whether they might develop age-dependent sleep alteration and RBD during prodromal period. A second sample of M83 mice received bilateral stereotaxic infusions of murine preformed a-Syn fibrils (mPFFs, van Andel Institute) into SLD to induce an additional synucleinopathy targeting REM sleep circuits. Mice were recorded every 2 weeks until occurrence of PD-like signs. Wake, Slow Wave Sleep and REM sleep were classified and quantified based on EEG/EMG signals. Our ongoing experiments indicate that control M83 mice started to experience RBD-like events at 9/10months age, characterized by sudden, rapid and jerky movements during REM sleep, easily distinguishable from those during Wake. A constant decrease with aging was noticed in daily PS amounts (from 91.0+/-2.8min to 64.8+/-1.3min at 5- and 9-months age). Of great interest, mPFFs-treated M83 mice also experienced intense RBD during REM sleep with a concomitant state fragmentation resulting from increased bout numbers of shorter duration, only 1-5 weeks after the recording start, likely with accelerated physio-pathological kinetics compared to that in control mice. As reported in patients, RBD may suppress REM sleep in M83 mice, especially when endowed with alteration of REM sleep circuits.
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Dates et versions

hal-04178071 , version 1 (07-08-2023)

Identifiants

  • HAL Id : hal-04178071 , version 1

Citer

Sébastien Arthaud, Maxime Grenot, Latifa Lakhdar, Thierry Baron, Patrice Fort. DEVELOPMENT OF A PRECLINICAL MODEL OF REM SLEEP BEHAVIOR DISORDER (RBD), A PRODROMAL PARASOMNIA OF PARKINSON’S DISEASE, IN M83 TRANSGENIC MICE. Neurofrance 2023, May 2023, LYON, France. ⟨hal-04178071⟩
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