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Introduction: Mental fatigue is a pervasive problem affecting cognitive performance, but its underlying mechanisms and effective measurement methods remain insufficiently understood. This study aims to examine the effects of cognitive load (high vs. low) and task duration (16 minutes vs. 32 minutes) on mental fatigue in healthy young adults using the Time Load Dual Back (TLDB) task.
Methods: Participants were divided into three groups based on task modality: Group 1 (low cognitive load, 16-minute task), Group 2 (low cognitive load, 32-minute task), and Group 3 (high cognitive load, 32-minute task). Objective performance measures (accuracy, reaction time, signal detection theory metrics) and subjective fatigue levels (measured via the Visual Analogue Scale of fatigue, VAS-f) were recorded before and after the task. The impact of task duration and cognitive load on these measures were analysed across groups using statistical methods. The deltas of the measurement scores were calculated to evaluate the impact of the time between the start and end of the task. Evaluation of task duration and workload were performed using t-tests for independent samples. Analyses for subjective measures (VAS-f) were performed using repeated measures ANOVA followed by post-hoc tests to analyse the differences between the groups. Pearson correlations were used to correlate objective and subjective measures.
Results: Regarding the analysis of the effect of task duration modulation on performance, changes in reaction times during the task were significantly different between groups. The shorter task duration was associated with faster reaction times. For performance changes based on workload, significant differences were observed between the high and low workload. Lower accuracy, as well as lower sensitivity and liberal response, were associated with the high workload. Reaction time was more significant in the long-duration, low-workload group. Measurements using the VAS-f showed a significant increase in scores between before and after the task for duration and workload analyses, with a significant interaction between time and group for the high workload. However, there were no significant results regarding group conditions. Correlation analyses for task duration showed no significant correlation between cognitive performance and VAS-f. Significant negative correlations were found for high workload between changes in accuracy and VAS-f. 
Conclusion: The study confirms that cognitive load is a key determinant of mental fatigue, with a higher workload leading to more pronounced declines in cognitive performance and a correlation with task accuracy and fatigue sensation. Task duration did not show significant differences between short and long durations. The TLDB task is validated as an effective tool for inducing and measuring mental fatigue in healthy young adults, except for reaction time, which showed contradictory results. Future research should explore more physiological and subjective measures to elucidate the underlying mechanisms of cognitive fatigue.

Sciences de la santé humaine > Neurologie

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Pediatric high-grade gliomas (pHGG) are the most aggressive gliomas in children, accounting for over 40% of brain tumor-related deaths in this population. The standard treatment involves surgical resection, when feasible, followed by radiotherapy and chemotherapy. Despite this combined ap-proach, the prognosis remains poor due to treatment resistance, leading to recurrences. This re-sistance is partially due to the presence of glioma stem cells (GSCs), which possess invasive capabili-ties and migrate towards the subventricular zone (SVZ), a neurogenic region active throughout life. Neural stem cells (NSCs) in this area interact with cerebrospinal fluid (CSF), secreted by the choroid plexuses. It is well known that the CSF influences NSCs in the SVZ, affecting neurogenesis. Recently, it has also been shown that CSF has a pro-tumoral role in adult glioblastoma (GBM).
The objective of this thesis was to study the influence of the choroid plexuses secretome on the phenotype of pHGG cells. As a surrogate for the CSF, a conditioned medium from choroid plexus epithelial cells was created and its impact on pHGG cells was analyzed. Optical microscopy revealed that this medium altered the morphology of tumor cells, making them more elongated, adherent, and forming intercellular connections. Flow cytometry analysis and cell counts showed no impact on tumor cell proliferation. The effect of this medium on the response to ONC201, a molecule in clini-cal trials, also showed no significant impact. However, migration/invasion assays using a Boyden chamber demonstrated a significant effect of the conditioned medium on the migratory and inva-sive abilities of pHGG cells. Finally, Western Blot analysis of various proteins (related to cell differen-tiation, adherence, invasion…), did not show any clear effect of the conditioned medium on cell fate. To conclude, the effect of patient-derived CSF from was analyzed, showing a tendency to de-crease pHGG cell proliferation and inducing a morphological change similar to that observed with the conditioned medium.
In summary, this study demonstrated the impact of a CSF surrogate model on the morphology and migration/invasion of pHGG cells, as well as the effect of CSF on cell morphology.

Sciences de la santé humaine > Neurologie

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Approximately 5% of the global population, or about 430 million people, are affected by hearing loss. Various factors can contribute to this hearing loss, including genetic differences, aging, prolonged exposure to loud noises, and the use of ototoxic medications. Certain anticancer drugs, such as cisplatin, and some antibiotics, such as aminoglycosides, are particularly harmful to the inner ear sensory cells, called the hair cells. Damage to these cells leads to permanent hearing loss since they cannot regenerate. Currently, no medication approved by the World Health Organization provides protection for the inner ear cells. Therefore, it is crucial to find molecules capable of preserving or restoring hearing. G protein-coupled receptors (GPCRs) play an important role in hearing, being involved in various cellular signaling pathways that regulate the function of hair cells. 
Our research project focuses on exploring the otoprotective potential of two GPCR antagonist molecules provided by Perha Pharmaceuticals. In the lab, we have previously demonstrated that the compounds 731 and 969 reduce the cytotoxic effect of cisplatin in hair cells. During my master thesis, we investigated if their otoprotective potential could also be demonstrated against gentamicin. For this purpose, we used two experimental models: an in vitro model with the HEI-OC1 cell line and an ex vivo model with explants of the mouse organ of Corti. Our results showed that in vitro, the molecule 731 increases cell survival in the presence of gentamicin when used at a concentration of 1 μM, while molecule 969 showed protective effects at both 1 μM and 10 μM. In the ex vivo model, only the molecule 969 demonstrated a protective effect at 1 nM. Additionally, our laboratory developed a knockout model for the GPCR targeted by these antagonists. Using the CRISPR-Cas9 method, mouse lines comprising two distinct deletions of 11 and 245 nucleotides were generated. The second objective of this thesis was to optimize genotyping strategies for these deletions. We thus tested various PCR conditions using different primer pairs, hybridization temperatures, and buffer conditions, along with the inclusion of an internal control.
Molecules 731 and 969 show potential for preserving cells from gentamicin-induced ototoxic damage; however, the survival outcome varies across experimental models and compound concentrations. Further studies, including in vivo tests, are essential to studying their efficacy and safety.

Oreille --- Ototoxicité --- Gentamicine --- Sciences de la santé humaine > Neurologie

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This feasibility and neurophysiological study aims to compare the effects of four types of stimulation - tDCS combined with music, tDCS combined with white noise, music alone (sham tDCS), white noise alone (sham tDCS) – on cognitive and neurophysiological outcomes in healthy participants, with the hypothesis that tDCS and music combined might improve cognitive functions (tested with the Stroop test and the 3-back test) compared to the other conditions, and thus, could be tested as a therapeutic option for patients with altered states of consciousness in the future. This study shows that in healthy subjects, a single session of tDCS combined with music does not increase cognitive functions, as hypothesized. Nonetheless, using music alone instead seems to be promising for increasing brain activity related to cognitive performances by means of an increase in frequencies associated with cognition. Even if the results might be promising, they come from a relatively small sample of 23 subjects and might not be sufficient to represent the general population.

tDCS, white noise, music, EEG, cognitive functions --- Sciences de la santé humaine > Neurologie

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Ce travail a évalué l’expression de marqueurs de la microglie et de cytokines dans le cerveau de cailles mâles et femelles au cours du développement ainsi que l’influence des œstrogènes sur ces mesures. L'objectif du projet était de comprendre le rôle de la microglie dans la différenciation sexuelle du cerveau. Pour cela, des RT-PCR sont réalisés sur des échantillons de cerveaux de caille.

Brain sexual differentiation --- Microglia --- Sex steroid hormones --- Quail --- Microglie --- Différenciation sexuelle du cerveau --- Inflammation --- Sciences de la santé humaine > Neurologie