Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons

Summary: We are reporting powerful streams of chromatin rupturing the nuclear envelope (NE) and the plasma membrane of migrating cerebral neurons in mouse embryos, which we suggest naming “piercing nuclear hernia” (PNH). About 40% of migrating neurons in cannabinoid type 1 receptor knock-out (CB1R−/...

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Main Authors: Yury M. Morozov, Pasko Rakic
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S258900422501449X
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author Yury M. Morozov
Pasko Rakic
author_facet Yury M. Morozov
Pasko Rakic
author_sort Yury M. Morozov
collection DOAJ
description Summary: We are reporting powerful streams of chromatin rupturing the nuclear envelope (NE) and the plasma membrane of migrating cerebral neurons in mouse embryos, which we suggest naming “piercing nuclear hernia” (PNH). About 40% of migrating neurons in cannabinoid type 1 receptor knock-out (CB1R−/−) mouse embryos and in wildtype embryos exposed to CB1R agonists show NE rupture and/or PNH. This indicates that deviations from optimal functioning of the endocannabinoid system in under- or over-activity may trigger analogous mechanisms increasing intranuclear pressure and chromatin herniation. The cells from CB1R−/− embryos showed pronounced ultrastructural disorders, such as high volume of herniated chromatin, mitochondrial fission, and negative correlation of the mitochondrial length with the volume of herniated chromatin. Catastrophic rupture of the nuclear and plasma membranes may provoke accidental cell death. At the same time, a fraction of neurons with PNH showed generally normal ultrastructure, which could indicate a mechanism of cell body repair.
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spelling doaj-art-9495c03f1bc44cf9bfaf8b7928f14bc52025-08-20T04:00:34ZengElsevieriScience2589-00422025-08-0128811318810.1016/j.isci.2025.113188Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neuronsYury M. Morozov0Pasko Rakic1Department of Neuroscience, Yale University School of Medicine and Kavli Institute for Neuroscience, New Haven, CT 06510, USA; Corresponding authorDepartment of Neuroscience, Yale University School of Medicine and Kavli Institute for Neuroscience, New Haven, CT 06510, USASummary: We are reporting powerful streams of chromatin rupturing the nuclear envelope (NE) and the plasma membrane of migrating cerebral neurons in mouse embryos, which we suggest naming “piercing nuclear hernia” (PNH). About 40% of migrating neurons in cannabinoid type 1 receptor knock-out (CB1R−/−) mouse embryos and in wildtype embryos exposed to CB1R agonists show NE rupture and/or PNH. This indicates that deviations from optimal functioning of the endocannabinoid system in under- or over-activity may trigger analogous mechanisms increasing intranuclear pressure and chromatin herniation. The cells from CB1R−/− embryos showed pronounced ultrastructural disorders, such as high volume of herniated chromatin, mitochondrial fission, and negative correlation of the mitochondrial length with the volume of herniated chromatin. Catastrophic rupture of the nuclear and plasma membranes may provoke accidental cell death. At the same time, a fraction of neurons with PNH showed generally normal ultrastructure, which could indicate a mechanism of cell body repair.http://www.sciencedirect.com/science/article/pii/S258900422501449XBiological sciencesCellular neuroscienceDevelopmental neuroscienceNatural sciencesNeuroscience
spellingShingle Yury M. Morozov
Pasko Rakic
Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
iScience
Biological sciences
Cellular neuroscience
Developmental neuroscience
Natural sciences
Neuroscience
title Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
title_full Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
title_fullStr Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
title_full_unstemmed Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
title_short Abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
title_sort abnormalities of the endocannabinoid system produce piercing nuclear hernias in migrating cerebral neurons
topic Biological sciences
Cellular neuroscience
Developmental neuroscience
Natural sciences
Neuroscience
url http://www.sciencedirect.com/science/article/pii/S258900422501449X
work_keys_str_mv AT yurymmorozov abnormalitiesoftheendocannabinoidsystemproducepiercingnuclearherniasinmigratingcerebralneurons
AT paskorakic abnormalitiesoftheendocannabinoidsystemproducepiercingnuclearherniasinmigratingcerebralneurons