The endocannabinoid system regulates synaptogenesis in a cortical spheroid model of fetal neurodevelopment / by Alexis Rose Papariello.
| Author/creator | Papariello, Alexis Rose author. |
| Format | Theses and dissertations |
| Publication | [Greenville, N.C.] : [East Carolina University], 2021. |
| Description | 1 online resource (152 pages) : illustrations (chiefly color). |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Other author/creator | Taylor, David A., degree supervisor. |
| Other author/creator | Litwa, Karen, degree supervisor. |
| Other author/creator | Soderstrom, Ken, degree supervisor. |
| Other author/creator | East Carolina University. Department of Pharmacology and Toxicology. |
| Series | ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED |
| Summary | The endocannabinoid system plays a complex role in synaptogenesis and the subsequent development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 controls synaptic strength at both excitatory and inhibitory synapses and thus contributes to the balance of excitatory and inhibitory signaling. Imbalances in the ratio of excitatory to inhibitory synapses have been implicated in various neuropsychiatric disorders associated with dysregulated central nervous system development including autism spectrum disorder, epilepsy, and schizophrenia. The role of the endocannabinoid system in human brain development has been difficult to study but advances in induced pluripotent stem cell technology have allowed us to model the fetal brain environment. Our cortical spheroid model resembles the cortex of the dorsal telencephalon during mid-fetal gestation and possesses functional synapses and spontaneous activity. Using SR141716A, we observed an increase in excitatory, and to a lesser extent, inhibitory synaptogenesis as measured by confocal image analysis. We also observed increased variability of neural activity and decreased GTPase RhoA activity. Overall, we have established that cortical spheroids express ECS components and are thus a useful model for exploring endocannabinoid mediation of childhood neuropsychiatric disease. |
| General note | Presented to the faculty of the Department of Pharmacology and Toxicology |
| General note | Advisor: David Taylor |
| General note | Advisor: Karen Litwa |
| General note | Advisor: Ken Soderstrom |
| General note | Title from PDF t.p. (viewed July 6, 2022). |
| Dissertation note | Ph. D. East Carolina University 2021 |
| Bibliography note | Includes bibliographical references. |
| Technical details | System requirements: Adobe Reader. |
| Technical details | Mode of access: World Wide Web. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Electronic Resources | Access Content Online | ✔ Available |