LIFESPAN SLEEP ALTERATION IN MICE
MODELLING THE HUMAN NEUROMELANIN
ACCUMULATION IN CATECHOLAMINERGIC
NEURONS

Sébastien Arthaud, Jean-Christophe Comte, Jiong Liu, Núria Peñuelas, Anna

Lagunas, Miquel Vila, Patrice Fort

► To cite this version:

Sébastien Arthaud, Jean-Christophe Comte, Jiong Liu, Núria Peñuelas, Anna Lagunas, et al.. LIFESPAN SLEEP ALTERATION IN MICE MODELLING THE HUMAN NEUROMELANIN ACCUMULATION IN CATECHOLAMINERGIC NEURONS. Neurofrance 2025, May 2025, Montpellier, France. 2025. [hal-05119338](https://hal.science/hal-05119338v1)

HAL Id: hal-05119338

https://hal.science/hal-05119338v1

Submitted on 19 Jun 2025

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**Reference:** AS-NF-2025-00480

**Title:** LIFESPAN SLEEP ALTERATION IN MICE MODELLING THE HUMAN NEUROMELANIN ACCUMULATION IN CATECHOLAMINERGIC NEURONS

**Preferred presentation type:** I submit my abstract for a poster presentation

**Authors:** S. Arthaud¹, J.-C. Comte², J. Liu¹, N. Penuelas³, A. Laguna³, M. Vila³, ⁴, ⁵, P. Fort¹
¹University Claude bernard, Lyon 1, Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Sleep Team, BRON, France, ²University Claude Bernard, Lyon 1, Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Forgetting Team, BRON, France, ³Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain, ⁴Autonomous University of Barcelona, Department of Biochemistry and Molecular Biology, Barcelona, Spain, ⁵Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

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**General data**

**Topic:** * Cognitive, affective and behavioral neuroscience, neuroethology

**2nd Topic:** Neurological and psychiatric diseases, experimental therapeutics

**Abstract text**

**Abstract text:** * Parkinson's disease (PD) is linked to the preferential degeneration of neurons that accumulate during lifespan the dark-brown cytoplasmic pigment neuromelanin (NM), as the catecholaminergic neurons in locus coeruleus (LC) and substantia nigra (SN). Since NM is not naturally produced in rodents, a mouse line was generated using the tissue-specific constitutive expression of human NM-synthesizing enzyme tyrosinase under the tyrosine hydroxylase promoter (TgNM). Mimicking human NM build-up in catecholaminergic cell groups, TgNM mice exhibit an early cell loss in LC that precedes cell dysfunction in SN concomitant to functional damages, founding a preclinical model with age-related neurodegenerative deficits (Laguna et al., Nat Com, 2024). Here we assessed whether TgNM mice, with a progressive decline of central catecholaminergic signaling, develop sleep alteration, including REM sleep behavior disorder associated to a reduced NM signal within LC area in multimodal magnetic resonance imaging in PD patients.

TgNM and WT mice were prepared for polysomnography (8 months) and recorded every 3 weeks until natural death of TgNM ones occurring 3 months earlier than WT congeners. Vigilance states were scored as Waking, non-REM and REM sleep based on EEG/EMG signals to quantify physiological parameters.

From the first polysomnographic recordings, TgNM mice depicted alterations in sleep microarchitecture (ultradian and circadian rhythms), as drastic reduced daily numbers of microarousals and short non-REM bouts and hypersomnia during active period. Non-parametric non-linear regression method combined to a general additive mixed model showed that sleep alterations were maintained with aging, without recovery nor significant aggravation. EEG analyses will help to determine whether sleep quality is also affected in TgNM (vs. WT) mice. Of physio-pathological interest, in-depth longitudinal EMG analyzes reveal that TgNM mice never exhibited REM sleep without atonia or RBD-like behavior at any ages.

In conclusion, TgNM mice depict alteration of sleep microarchitecture occurring early in the process of NM build-up in catecholaminergic neurons, without recovery nor aggravation with aging. This suggests an early impact of LC neurodegeneration (rather than SN) in this premature-like sleep phenotype. This further highlights the major contribution of LC neurons in the physiological fine-tuning of sleep, and likely in sleep disorders reminiscent of neurodegenerative diseases as PD.

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