Exploration des origines des anomalies de l'électrorétinogramme chez les patients atteints de maladies psychiatriques : des biomarqueurs potentiels des maladies du cerveau
|Advisor:||Hébert, Marc; Beaulieu, Jean Martin|
|Abstract:||One of the major obstacles in psychiatry is the difficult access to the functioning brain to better understand the biological underpinning of brain disorders. There is a need to develop new approaches to study the neurological functions indirectly. Since the retina is part of the central nervous system, it had been suggested that retinal functions, as measured with the electroretinogram (ERG), may reflect the central dysfunctions reported in psychiatric disorders. In fact, several ERG anomalies, which may serve as biomarkers, have been observed in people with or at risk of psychiatric disorders, such as seasonal affective disorder (SAD) and schizophrenia. However, the origins of these ERG anomalies remain elusive and the goal of this thesis is to explore the potential molecular underpinning of these ERG deficits with animal models of psychiatric disorders or the use of a pharmacological agent. Because of their well-described involvement in psychiatric disorders, the targeted molecules of the experiments presented in this thesis are melatonin, central dopamine, central serotonin and glycogen synthase kinase-3 (GSK3). The first study demonstrates that a dysfunction in melatonin secretion may partially be involved in the ERG anomalies observed in people with SAD. The second study is a complement of the first one and reports that impairments in central serotonin and central dopamine neurotransmission are more likely to be involved in the ERG anomalies observed in patients with SAD than changes in the retinal bioavailability of dopamine receptors D1R and D2R. A multifactorial model of the ERG anomalies in people with SAD has been proposed according to the findings of these two previous studies. Moreover, the third study demonstrates that GSK3 overexpression, which is a risk factor for schizophrenia and bipolar disorder, replicates the ERG anomaly reported in offspring at high genetic risk for these disorders. Finally, the fourth study demonstrates that GSK3 plays an important role in regulating the biological clock. Overall, this thesis suggests that ERG measurements represent a useful tool in psychiatric research.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||20 April 2018|
|Collection:||Thèses et mémoires|
All documents in CorpusUL are protected by Copyright Act of Canada.