Study of the role of alterations in the wake/sleep cycles in the progression of Parkinson's disease and multiple system atrophy ; Etude du rôle des altérations des cycles éveil/sommeil dans la progression de la maladie de Parkinson et de l'atrophie multisystématisée
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Media type:
E-Book
Title:
Study of the role of alterations in the wake/sleep cycles in the progression of Parkinson's disease and multiple system atrophy ; Etude du rôle des altérations des cycles éveil/sommeil dans la progression de la maladie de Parkinson et de l'atrophie multisystématisée
Published:
[Erscheinungsort nicht ermittelbar]: HAL CCSD, 2021
Language:
French
Origination:
University thesis:
Dissertation, HAL CCSD, 2021
Footnote:
Description:
Parkinson's disease (PD) and Multiple System Atrophy are both synucleinopathies. These diseases are characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) and the presence of cytoplasmic inclusions. These inclusions are named Lewy Bodies (LB) in PD and glial cytoplasmic inclusions (GCI) in MSA and contain notably misfolded alpha-synuclein ( syn). In addition to movement disorders, PD and MSA patients exhibit a myriad of non-motor symptoms including sleep/wake alterations that may occur early in the course of the diseases and that are even considered as predictors of synucleinopathies. The aim of my thesis is thus to investigate the likelihood of a relationship between the progression of neurodegeneration, the progression of the syn pathology, and the occurrence of sleep/wake issues.First of all, as the degeneration of the dopamine system is a critical feature in synucleinopathies, we wanted to record sleep in conditions of dopamine depletion. Sleep in mice was recorded after the injection of reserpine and alpha-methyltyrosine. This first drug strongly reduces stores of monoamine neurotransmitters, including dopamine. The second drug inhibits the tyrosine hydroxylase and thus the synthesis of dopamine.While neurotoxin-based experimental models recapitulate both motor and non-motor symptoms of PD, their poor face validity concerning the neurodegenerative process makes them unsuitable for this project. We here take advantage of recently developed LB mouse and LB monkey models of parkinsonian degeneration. These models are well adapted to examine the potential occurrence of sleep/wake deficits as the pathology progresses slowly over time and is based on a-syn pathology. Wild-type mice were injected in the SNc with LB fractions (LB mice), containing pathological α syn. These fractions are extracted from the brain of PD patients and, once injected, lead to a progressive loss of DA neurons. Control mice were injected with sucrose. Mice were then implanted with a device ...