Evolution of the sleep-waking cycle in transgenic mice with an age-dependent accumulation of neuromelanin in catecholaminergic neurons, a new humanized model of Parkinson’s Disease - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2022

Evolution of the sleep-waking cycle in transgenic mice with an age-dependent accumulation of neuromelanin in catecholaminergic neurons, a new humanized model of Parkinson’s Disease

Résumé

Parkinson’s disease (PD) is characterized by a preferential degeneration of neurons accumulating with age neuromelanin in PD-vulnerable areas as substantia nigra (SN) and locus coeruleus (LC). Since this pigment is not naturally produced in most animals including rodents, we recently generated a neuromelanin-producing mouse model based on the tissue-specific constitutive expression of melanin-producing enzyme tyrosinase under the tyrosine hydroxylase promoter (Tg-TH-Tyr). As in humans, these animals age-dependently accumulate neuromelanin within catecholaminergic neurons. In parallel to its intracellular buildup, Tg-TH-Tyr mice exhibit an early degeneration of noradrenergic LC neurons that precedes nigral dopaminergic dysfunction, equivalent to prodromal PD, as well as PD-like motor and non-motor (i.e. olfactory, cognitive) deficits. Here we assessed whether Tg-TH-Tyr mice may also exhibit sleep alteration and REM sleep behaviour disorder (RBD), two documented prodromal manifestations of PD, likely linked to a degeneration of the LC/subcoeruleus area critical for REM sleep. For this goal, Tg-TH-Tyr and WT littermate mice (5 months old), prepared for polysomnography and video, were recorded for 58 weeks until natural death (5 Tg-6 WT). Preliminary results evidenced modifications of daily amounts and bout numbers of REM sleep, as their circadian distribution in Tg-TH-Tyr vs. WT mice, independently of the age factor. While clear occurrence of RBD was not detected by rapid video scrutinization, ongoing analyses of both EMG and EEG signals will allow to determine whether tonic/phasic motor events during REM sleep and the overall sleep quality are differentially affected by aging, along the presymptomatic PD period, in Tg-TH-Tyr vs. WT mice.
Fichier non déposé

Dates et versions

hal-04176874 , version 1 (03-08-2023)

Identifiants

  • HAL Id : hal-04176874 , version 1

Citer

Sébastien Arthaud, Jiong Liu, Nuria Peñuelas, Ariadana Laguna, Miquel Vila, et al.. Evolution of the sleep-waking cycle in transgenic mice with an age-dependent accumulation of neuromelanin in catecholaminergic neurons, a new humanized model of Parkinson’s Disease. FENS Forum, Jul 2022, PARIS, France. ⟨hal-04176874⟩
5 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More