Grant: Master's Award: Canada Graduate Scholarships

Approximately 5 million adult Canadians meet the criteria for a mood, anxiety, or substance abuse disorder. However, psychiatry suffers from a lack of adequate treatments. Recently, research has shifted to the promising potential of psychedelic compounds. Serotonergic psychedelics, including lysergic acid diethylamide (LSD), demonstrate clinical efficacy for post-traumatic stress disorder and treatment-resistant depression, amongst other mood disorders. Neuroimaging studies in humans receiving LSD reveal the compound's ability to induce significant brain changes, notably through modifying functional organization and network dynamics. Myelin, a protective sheath made by oligodendrocytes, is important for efficient electrical transmission along nerve cells and is essential to brain health and function. At the cellular and molecular levels, there is a strong association between abnormalities in myelination and cognitive impairments as well as depression-like symptoms. Individuals with poor mood regulation have reduced structural integrity of their white matter tracts, which is supported by evidence demonstrating that reduced cortical myelination correlates with depressive disorders. LSD may modulate myelin directly through serotonin-based interactions with oligodendrocytes, or indirectly via other glial cells. This study aims to decipher the impact of chronic low-dose LSD on myelination in a stress-induced mouse model of depression. We will assess the myelination ratio at internodes and the effects of LSD on cellular stress markers amongst oligodendrocyte lineage cells in mice exposed to chronic restraint stress. Focusing on myelin following the administration of LSD will unveil the underlying mechanisms of psychedelics and offer insights for upcoming clinical studies.