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.
Description1 online resource (152 pages) : illustrations (chiefly color).
Supplemental ContentAccess via ScholarShip
Subjects

Other author/creatorTaylor, David A., degree supervisor.
Other author/creatorLitwa, Karen, degree supervisor.
Other author/creatorSoderstrom, Ken, degree supervisor.
Other author/creatorEast Carolina University. Department of Pharmacology and Toxicology.
SeriesECU 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 notePresented to the faculty of the Department of Pharmacology and Toxicology
General noteAdvisor: David Taylor
General noteAdvisor: Karen Litwa
General noteAdvisor: Ken Soderstrom
General noteTitle from PDF t.p. (viewed July 6, 2022).
Dissertation notePh. D. East Carolina University 2021
Bibliography noteIncludes bibliographical references.
Technical detailsSystem requirements: Adobe Reader.
Technical detailsMode of access: World Wide Web.
Genre/formAcademic theses.
Genre/formAcademic theses.
Genre/formThèses et écrits académiques.

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