Interneuron migration impairment and brain region-specific DNA damage response following irradiation during early neurogenesis in mice DOI Creative Commons
Lisa Berden, Nicholas Rajan,

André Claude Mbouombouo Mfossa

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Март 17, 2025

Abstract Embryonic DNA damage resulting from repair deficiencies or exposure to ionizing radiation during early neurogenesis can lead neurodevelopmental disorders, including microcephaly. This has been linked an excessive response in dorsal neural progenitor cells (NPCs), p53-dependent apoptosis and premature neuronal differentiation which culminates depletion of the NPC pool. However, effect on ventral forebrain NPCs, origin interneurons, remains unclear. In this study, we investigated sequelae irradiation mouse fetuses at timepoint neurogenesis. We focused neocortex (NCX) medial ganglionic eminence (MGE), key regions for developing respectively. Although both showed a typical p53-mediated consisting cell cycle arrest, apoptosis, NCX displayed prolonged while MGE exhibited more sustained apoptosis. Moreover, reduced migration speed interneurons acute living brain slices explants, latter indicating cell-intrinsic component defect. RNA sequencing protein analyses revealed disruptions actin microtubule cytoskeletal-related cellular machinery, particularly cells. Despite massive obvious interneuron defect, prenatally irradiated animals did not show increased sensitivity pentylenetetrazole-induced seizures, nor was there reduction cortical young adult mice. suggests high plasticity insults Overall, our findings indicate that embryonic induces region-specific responses, potentially disorders.

Язык: Английский

Aberrant choroid plexus formation drives the development of treatment-related brain toxicity DOI Creative Commons
Tamara Bender,

Esther Schickel,

Celine Schielke

и другие.

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Фев. 22, 2025

Abstract Brain tumors are commonly treated with radiotherapy, but the efficacy of treatment is limited by its toxicity to normal tissue including post-irradiation contrast enhanced lesions often linked necrosis. The poorly understood mechanisms behind such brain were studied using cerebral organoids. Here we show that irradiation organoids leads dose-dependent growth retardation and formation liquid-filled cavities not correlated Instead, radiation-induced changes comprise an enhancement cortical hem markers, altered neuroepithelial stem cell differentiation, increase ZO1 + /AQP1 /CLDN3 -choroid plexus (CP)-like structures accompanied upregulation IGF2 mRNA, known be expressed in CP cerebrospinal fluid. differentiation attributed WNT/BMP signaling pathways. We conclude aberrant can involved providing additional strategies for possible countermeasures.

Язык: Английский

Процитировано

0
Interneuron migration impairment and brain region-specific DNA damage response following irradiation during early neurogenesis in mice DOI Creative Commons
Lisa Berden, Nicholas Rajan,

André Claude Mbouombouo Mfossa

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Март 17, 2025

Abstract Embryonic DNA damage resulting from repair deficiencies or exposure to ionizing radiation during early neurogenesis can lead neurodevelopmental disorders, including microcephaly. This has been linked an excessive response in dorsal neural progenitor cells (NPCs), p53-dependent apoptosis and premature neuronal differentiation which culminates depletion of the NPC pool. However, effect on ventral forebrain NPCs, origin interneurons, remains unclear. In this study, we investigated sequelae irradiation mouse fetuses at timepoint neurogenesis. We focused neocortex (NCX) medial ganglionic eminence (MGE), key regions for developing respectively. Although both showed a typical p53-mediated consisting cell cycle arrest, apoptosis, NCX displayed prolonged while MGE exhibited more sustained apoptosis. Moreover, reduced migration speed interneurons acute living brain slices explants, latter indicating cell-intrinsic component defect. RNA sequencing protein analyses revealed disruptions actin microtubule cytoskeletal-related cellular machinery, particularly cells. Despite massive obvious interneuron defect, prenatally irradiated animals did not show increased sensitivity pentylenetetrazole-induced seizures, nor was there reduction cortical young adult mice. suggests high plasticity insults Overall, our findings indicate that embryonic induces region-specific responses, potentially disorders.

Язык: Английский

Процитировано

0