As the prevalence of Parkinson’s disease is expected to increase gradually over the years based on recent scientific predictions, developing a treatment plan to mitigate the development of this disease is essential. Previous research tried to tackle the motor and non-motor symptoms associated with the disease. That said, some symptoms seem to persist, and the quality of life of PD patients continues to decline. Zebrafish have emerged as a strong model to study the regeneration of DAergic neurons as they have the ability to show robust adult neurogenesis. Here, we used adult zebrafish to investigate DAergic neuron regeneration following ablation in various brain regions. In addition, we tested the efficacy of Nifurpirinol, an alternative substrate to MTZ, in ablating DAergic neurons in the adult zebrafish brain. Lastly, we tracked how the ablation of DAergic neurons influences the motor activity of adult zebrafish and how they tend to recover over time. Results showed a significant reduction in DAergic neurons at 7 days following the MTZ treatment in the olfactory bulb, telencephalon, and the periventricular pretectal nucleus. NFP also caused similar changes, albeit they were less statistically significant. In response to ablated DAergic neurons, MTZ-treated fish showed a significant increase in the number of neural stem cells undergoing proliferation at 1 dpt. However, the highest spike in proliferative cells, especially neural stem cells, was found at 7 dpt. This time point corresponded with the greatest decrease in DAergic neurons following ablation. These cellular changes were observed in the olfactory bulb and the telencephalon. That said, more drastic changes were noticed in the rostral and medial telencephalon. Results also showed that the adult zebrafish brain was not able to significantly replenish the number of DAergic neurons as early as 15 dpt. Based on previous observations, it seems that adult zebrafish need at least 45 days to regenerate their DAergic neurons to levels comparable to the DMSO control. Lastly, behaviour analysis showed that NFP has the most significant impact on motor activity across three different parameters at 0 hpt. MTZ also had similar effects on motor activity; however, it was less pronounced. The impact on the behaviour level seems more transient as some recovery was observed at 7 dpt. Overall, this transgenic zebrafish line allowed us to explore how and when the adult zebrafish brain was able to efficiently recover following the specific ablation of DAergic neurons. In addition, it expanded our understanding of adult neurogenesis which will hopefully allow us to better approach patients with Parkinson’s disease.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/42798 |
| Date | 08 October 2021 |
| Creators | Abu Setah, Samy |
| Contributors | Ekker, Marc |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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