Hippocampal neurogenesis is linked to the onset, progression and remission of major mood disorder such as anxiety and depression. Neurogenesis is the process by which new neurons are formed in the brain. Mitochondria mediate cellular adaption and provide energy to support growth of new neurons. Chronic stress and mood disorders have been associated with impairments in mitochondrial function and neuronal growth. Individuals experiencing stress and mood disorders reportedly use cannabis as a means to self-medicate. The impacts of cannabis on stress-related effects on hippocampal neurogenesis and mitochondria are vastly unexplored. To investigate these effects we generated an in vitro model of hippocampal neuron stress by treating HT22 cells with corticosterone, the major effector molecule of stress in rodents. We first characterized the impacts of corticosterone on markers of neurogenesis and mitochondrial function in HT22 hippocampal cells. We found that corticosterone decreased gene markers of neurogenesis, mitochondrial biogenesis, content, dynamics and decreased mitochondrial membrane potential. Corticosterone also decreased levels of antioxidant enzymes but did not alter levels of reactive oxygen species (ROS) or elicit lipid peroxidation. We then investigated with potential impacts of cannabis components, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on corticosterone-induced stress. Individually, THC and CBD decreased markers of neurogenesis, dysregulated mitochondrial dynamics and decreased mitochondrial membrane potential. Interestingly, both THC and CBD increased a marker of mitochondrial biogenesis. Finally, we co-treated HT22 cells with corticosterone and THC or CBD to interrogate the impacts of THC and CBD on corticosterone-induced alterations. Our results indicated THC and CBD had no effect on corticosterone-related reductions in neurogenesis markers or mitochondrial membrane potential. However, THC demonstrated a rescuing effect on a marker of mitochondrial biogenesis and CBD normalized a marker of mitochondrial fission; both of which were decreased with individual corticosterone treatments. This thesis ultimately identifies some of the pathways THC and CBD may impact stress response in relation to neurogenesis and mitochondria. / Thesis / Master of Science (MSc) / Neurogenesis is a process that describes the production of new nerve cells in the brain. It mainly occurs during early life, but persists in a central brain structure responsible for learning and memory, known as the hippocampus, throughout our lives. This active brain structure relies on the function of certain organelles called mitochondria, which are the primary cellular energy producers and promote nerve cell production. Mood disorders, such as anxiety and depression, may result as a consequence of impaired hippocampal neurogenesis. Evidently, people suffering from anxiety and depression turn to cannabis use for management and treatment of their mood disorders. Considering cannabis has been shown to affect neurogenesis and mitochondrial function, our primary objective was to explore its effects on hippocampal neurogenesis by focusing on mitochondrial function, in the context of stress. We demonstrate that components found in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), alter the stress-induced changes in mitochondrial functions related to neurogenesis, suggesting that cannabis may play a role in protecting nerve cells.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28935 |
| Date | 11 1900 |
| Creators | MacAndrew, Andie |
| Contributors | Raha, Sandeep, Medical Sciences (Cell Biology and Metabolism) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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