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Chronic stress is an increasing cause for concern in modern society. Stress is an evolutionary mechanism allowing adaptation to urgent situations. However, in western lifestyle, stress has become a burden, which is often associated to disease, including mental and behavioral disruption. Additionally, stress seems having a wide range of effects that could impact the offspring as well. For instance, impaired reproduction and sexual behavior have been reported to be the possible result of exposure to prenatal stress. Based on this, we aimed to investigate the permanent effects of prenatal stress on female and male offspring’s sexual behavior.
To induce prenatal stress, pregnant dams were submitted to restrain stress from the second to delivery day. Thereafter, pups were not undisturbed until they reached adulthood (8 weeks) where they were finally tested. Mice were put through elevated plus maze test and blood sampling, to assess for the behavioral and physiological manifestations of stress. Blood samples were collected in two conditions, home cage and 30 min following the EPM test to evaluate the functioning of the HPA axis with assessment of corticosterone and DHEA. Vaginal smear assay was performed on female to investigate their estrous cycling. Sexual performance was tested on both virgin females and males, then partner preference test was performed on both sexes to assess for the sexual preference. 
Our results show that anxiety and the level of stress hormones were not particularly altered in prenatally stressed females, while the males seemed to have developed resistance and reduced reactivity to stress. In fact, we observed low corticosterone response upon exposure to EPM test and low basal DHEA levels. Regarding sexual behavior, prenatally stressed females and males demonstrated similar sexual performance compared to control groups. Also, we noted that prenatal stress significantly impacted sexual preference in both female and male. These observations not only show that prenatal stress impacted male and female offspring but also that some effects were sexually dimorphic. 
In conclusion, prenatal stress is an increasingly wording issue that has generational repercussions. In our study we chose to evaluate the impact of prenatal stress in female and male offspring. While anxious behavior and sexual performance were affected only in males, sexual preference seemed altered in both sexes.

stress, corticosterone, sexual behavior, mate preference, anxiety --- Sciences de la santé humaine > Neurologie

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Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly. Although it was discovered in the early 1900's, no disease-modifying treatment has been discovered to cure this disease and the pathogenesis still remains enigmatic. Current animal models of the disease cannot recapitulate all hallmarks present in the brains of AD patients. Human pluripotent stem cells (hPSC) whether isolated from the embryo (human embryonic stem cell, hESC) or reprogrammed from somatic cells from a donor (human induced pluripotent stem cells, hiPSC) are an unlimited source of cells that can be differentiated into any cell types of the body. hPSC can therefore be used to generate cell types such as brain cells as models to advance our knowledge in AD.
In this project, I generated three reprogrammed hiPSC lines derived from three different familial AD (FAD) patients. These hiPSC lines were validated for pluripotency by immunofluorescence experiments and quantitative PCR to detect the expression of stemness genes. Moreover, I used these hiPSC lines to differentiate spontaneous embryoid bodies that are composed of cells derived from any of the three germ layers of an embryo: endoderm, mesoderm and ectoderm. All these experiments confirmed the pluripotency of the hiPSC lines generated. In the next part, I generated cortical brain organoids from wild type hESC and transgenic hESC transduced with the human amyloid precursor protein (APP) carrying FAD mutations. Brain organoids were analysed and characterized for the presence of AD hallmarks in vitro. I confirmed that human brain organoids derived from AD hESC express higher levels of APP. Interestingly, AD hESC-derived organoids revealed some differences related to cortical layer identity as well as lower levels of expression of maturation markers and higher levels of expression of glial markers. Finally, I have observed that AD hESC-derived brain organoids showed increased Tau phosphorylation levels, a major AD hallmark.
Overall, this suggests that this model is of potential interest for the study of Alzheimer's disease.

Alzheimer’s disease --- Human pluripotent stem cells --- Brain organoid models --- Sciences de la santé humaine > Neurologie

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Suite à un accident cérébral grave, les patients peuvent évoluer d’un coma (patient non-éveillable et inconscient), vers un état végétatif/syndrome d’éveil non-répondant (patient éveillé mais inconscient), vers un état de conscience minimale (patient éveillé et conscient, mais non-communiquant), ou un locked-in syndrome (patient éveillé, conscient, mais ne pouvant exprimer sa conscience que par le biais de mouvements oculaires). L’attribution d’un diagnostic différentiel suite aux évaluations cliniques à l’aide d’échelles comportementales peut se révéler extrêmement complexe avec un taux d’erreurs diagnostiques pouvant toucher plus de 4 patients sur 10 (Childs, Mercer, & Childs, 1993; Schnakers, Vanhaudenhuyse, Giacino, Ventura, Boly et al., 2009c). Afin d’affiner ce dernier, un vaste champ de recherche s’est créé ayant pour but le développement d’outils objectifs complémentaires à l’examen comportemental clinique. Nous avons proposé ici l’utilisation du sniff controller, une toute nouvelle technique permettant de détecter des signes de conscience a l’aide du contrôle volontaire de la respiration. Notre paradigme, utilisé pour la première fois auprès de patients atteints de trouble de la conscience, avait pour but de demander aux patients de moduler volontairement leur respiration afin de dépasser un seuil prédéfini. Selon les résultats obtenus, il semble que le sniff controller, moyennant plus d’essais et certaines modifications à apporter au système et au paradigme, pourrait se révéler être un outil complémentaire dans l’évaluation para-clinique de ces patients. En effet, l’utilisation de ce système pourrait se révéler comme plus sensible à la détection de réponse à la commande que les évaluations comportementales. De plus, il s’agit d’une interface peu dispendieuse, relativement simple d’utilisation, transportable au chevet du patient et tout à fait non-invasive.

Personnes atteintes de lésions cérébrales --- Conscience --- Examens médicaux --- Sciences de la santé humaine > Neurologie --- Sciences sociales & comportementales, psychologie > Neurosciences & comportement --- Sciences sociales & comportementales, psychologie > Traitement & psychologie clinique

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Sleeping is a fundamental behavior that occupies almost a third of our lives. Its physiological importance is therefore easily understood. Scientific evidence of the role of quality sleep for healthy cognitive aging is accumulating. Many studies have shown the association between sleep dysfunction and Alzheimer's disease (AD). Interestingly, a significant aspect of AD is that its primary pathophysiological sign is detected post-mortem before the age of 35 years in the locus coeruleus (LC) which is a small brainstem nucleus essential for sleep regulation. Thus, there are some reasons to establish early associations between sleep and AD via the LC. However, the link between variability in sleep quality and variability in LC characteristics remains poorly understood in humans. Therefore, it seems appropriate to first study the link between sleep and LC characteristics such as its reactivity. In this context, we postulate that a greater LC reactivity during wakefulness is associated with a better sleep, during youth as well as throughout the aging process. To test this hypothesis, young (18-29 years, n = 13) and older subjects (53-69 years, n = 14) were recruited. On the one hand, we worked with electroencephalography to characterize sleep, on the other hand, we used ultra-high field MRI (7 Tesla) to assess LC reactivity. The aim of this thesis was to highlight a link between sleep and LC reactivity during an auditory oddball task. Our results suggested for the first time in humans, a link which seems to change over the life course. Thus, in the youth, sleep seems to be more stable when the LC is more reactive, at least when this reactivity is assessed via an auditory oddball task.

Sleep, Alzheimer’s Disease, Locus Coeruleus Reactivity, Auditory Oddball Task, EEG, 7T MRI --- Sciences de la santé humaine > Neurologie --- Sciences sociales & comportementales, psychologie > Neurosciences & comportement

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Les expériences de mort imminente (EMI) sont des phénomènes complexes d’état de conscience modifié qui peuvent survenir lors de la perte de conscience consécutive à une menace pour la vie de l’individu. Bien que l’étude de ces phénomènes relève principalement de témoignages des individus, il apparait un certain nombre d’évènements récurrents tels que des émotions agréables, la vue d’un tunnel et/ou d’une lumière, la vue de proches décédés, une expérience de sortie du corps ou encore un retour conscient à l’intérieur du corps.

Certaines études neuroscientifiques sous-tendent que ces EMI peuvent être vécues par des individus atteints d’épilepsie, et ce durant leurs crises. Ces derniers seraient également à même d’expérimenter des phénomènes de décorporation si leurs crises provoquent une activation de certaines zones cérébrales, en particulier de la région temporo-pariétale. Afin d’investiguer plus en profondeur dans ce domaine, nous proposons d’étudier les interactions qu’il existe entre les EMI et l’épilepsie ainsi que la fréquence d’apparition de ces phénomènes chez des individus épileptiques. Pour ce faire, nous recruterons des patients épileptiques pris en charge au CHU de Liège, notamment par le Dr. Olivier Bodart. Ces patients seront soumis à divers questionnaires, d’une part standardisés, et d’autre part établis par nos soins afin d’obtenir un maximum d’informations sur leur vécu.

Expériences de mort imminente --- épilepsie --- neurosciences --- décorporation --- Near-Death Experiences --- Out-of-Body Experience --- epilepsy --- neurosciences --- Sciences de la santé humaine > Neurologie --- Sciences sociales & comportementales, psychologie > Neurosciences & comportement