CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development

Abstract The endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB1) controls synaptic strength at both excitatory and inhibitory synapses and thus contributes to the balance of excitatory and inhi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alexis Papariello, David Taylor, Ken Soderstrom, Karen Litwa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/031b40679be64efd93baa18274e47b41
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:031b40679be64efd93baa18274e47b41
record_format	dspace
spelling	oai:doaj.org-article:031b40679be64efd93baa18274e47b412021-12-02T17:39:30ZCB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development10.1038/s41598-021-88750-22045-2322https://doaj.org/article/031b40679be64efd93baa18274e47b412021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88750-2https://doaj.org/toc/2045-2322Abstract The endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB1) 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 CB1 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. Cortical spheroids resemble the cortex of the dorsal telencephalon during mid-fetal gestation and possess functional synapses, spontaneous activity, an astrocyte population, and pseudo-laminar organization. We first characterized the ECS using STORM microscopy and observed synaptic localization of components similar to that which is observed in the fetal brain. Next, using the CB1-selective antagonist SR141716A, we observed an increase in excitatory, and to a lesser extent, inhibitory synaptogenesis as measured by confocal image analysis. Further, CB1 antagonism increased the variability of spontaneous activity within developing neural networks, as measured by microelectrode array. Overall, we have established that cortical spheroids express ECS components and are thus a useful model for exploring endocannabinoid mediation of childhood neuropsychiatric disease.Alexis PaparielloDavid TaylorKen SoderstromKaren LitwaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexis Papariello David Taylor Ken Soderstrom Karen Litwa CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
description	Abstract The endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB1) 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 CB1 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. Cortical spheroids resemble the cortex of the dorsal telencephalon during mid-fetal gestation and possess functional synapses, spontaneous activity, an astrocyte population, and pseudo-laminar organization. We first characterized the ECS using STORM microscopy and observed synaptic localization of components similar to that which is observed in the fetal brain. Next, using the CB1-selective antagonist SR141716A, we observed an increase in excitatory, and to a lesser extent, inhibitory synaptogenesis as measured by confocal image analysis. Further, CB1 antagonism increased the variability of spontaneous activity within developing neural networks, as measured by microelectrode array. Overall, we have established that cortical spheroids express ECS components and are thus a useful model for exploring endocannabinoid mediation of childhood neuropsychiatric disease.
format	article
author	Alexis Papariello David Taylor Ken Soderstrom Karen Litwa
author_facet	Alexis Papariello David Taylor Ken Soderstrom Karen Litwa
author_sort	Alexis Papariello
title	CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
title_short	CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
title_full	CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
title_fullStr	CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
title_full_unstemmed	CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
title_sort	cb1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/031b40679be64efd93baa18274e47b41
work_keys_str_mv	AT alexispapariello cb1antagonismincreasesexcitatorysynaptogenesisinacorticalspheroidmodeloffetalbraindevelopment AT davidtaylor cb1antagonismincreasesexcitatorysynaptogenesisinacorticalspheroidmodeloffetalbraindevelopment AT kensoderstrom cb1antagonismincreasesexcitatorysynaptogenesisinacorticalspheroidmodeloffetalbraindevelopment AT karenlitwa cb1antagonismincreasesexcitatorysynaptogenesisinacorticalspheroidmodeloffetalbraindevelopment
_version_	1718379804721414144

CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development

Ejemplares similares