Article (Scientific journals)
The subventricular zone neurogenic niche provides adult born functional neurons to repair cortical brain injuries in response to diterpenoid therapy.
Pardillo-Díaz, Ricardo; Pérez-García, Patricia; Ortego-Domínguez, María et al.
2025In Stem Cell Research and Therapy, 16 (1), p. 1
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Keywords :
Brain repair therapy; Cortical brain injury; Diterpenoids; Morphofunctional properties; Neural stem cells; Neurogenesis; Neuronal differentiation; Newly generated neurons; Subventricular zone; Diterpenes; Animals; Mice; Cell Movement/drug effects; Cell Differentiation/drug effects; Stem Cell Niche/drug effects; Cerebral Cortex/drug effects; Cerebral Cortex/metabolism; Mice, Inbred C57BL; Diterpenes/pharmacology; Neurogenesis/drug effects; Neural Stem Cells/drug effects; Neural Stem Cells/metabolism; Neural Stem Cells/cytology; Neurons/drug effects; Neurons/metabolism; Brain Injuries/drug therapy; Brain Injuries/therapy; Brain Injuries/pathology; Brain Injuries/metabolism; Lateral Ventricles/drug effects; Lateral Ventricles/metabolism; Brain Injuries; Cell Differentiation; Cell Movement; Cerebral Cortex; Lateral Ventricles; Neurons; Stem Cell Niche; Medicine (miscellaneous); Molecular Medicine; Biochemistry, Genetics and Molecular Biology (miscellaneous); Cell Biology
Abstract :
[en] INTRODUCTION: Neural stem cells from the subventricular zone (SVZ) neurogenic niche provide neurons that integrate in the olfactory bulb circuitry. However, in response to cortical injuries, the neurogenic activity of the SVZ is significantly altered, leading to increased number of neuroblasts with a modified migration pattern that leads cells towards the site of injury. Despite the increased neurogenesis and migration, many newly generated neurons fail to survive or functionally integrate into the cortical circuitry. Providing the injured area with the adequate signaling molecules may improve both migration and functional integration of newly generated neurons. METHODS: In here, we have studied the effect of a diterpene with the capacity to induce neuregulin release at promoting neurogenesis in a murine model of cortical brain injury. Using green fluorescent protein expressing vectors we have labeled SVZ cells and have studied the migration of newly generated neuroblasts toward the injury in response the treatment. In addition, using electrophysiological recordings we have studied the differentiation of these neuroblasts into mature neurons and their functional integration into the cortical circuitry. We have studied their electrical properties, their morphology and cortical location. RESULTS: We have found that EOF2 treatment of adult mice with mechanical cortical injuries facilitates the delivery of neuroblasts into these injuries. The newly generated neurons develop features of fully functional neurons. Our results show that the newly generated neurons receive electrical inputs, fire action potentials, and undergo complete differentiation into neurons recapitulating the stages that distinguish ontogenic differentiation. These neurons develop features representative of neurons belonging the cortical layer in which they are situated. We have also studied that EOF2 facilitates neuregulin release in SVZ cells, a signaling factor that promotes neuronal differentiation. Neuregulin is expressed in microglial cells that reach the injury in response to the damage and its release is increased by EOF2 treatment. CONCLUSION: Promoting neuregulin release via diterpene treatment facilitates migration of SVZ-derived neuroblasts to cortical injuries stimulating their differentiation into mature functional neurons, which receive electrical inputs and develop features of cortical neurons. These findings highlight the role of diterpenoids as a potential therapy to repair cortical brain injuries.
Disciplines :
Biochemistry, biophysics & molecular biology
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Pardillo-Díaz, Ricardo;  Department of Physiology, University of Seville, Seville, Spain ; Division of Physiology, University of Cadiz, Cadiz, Spain ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain
Pérez-García, Patricia;  Department of Physiology, University of Seville, Seville, Spain ; Division of Physiology, University of Cadiz, Cadiz, Spain ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain
Ortego-Domínguez, María;  Department of Physiology, University of Seville, Seville, Spain ; Division of Physiology, University of Cadiz, Cadiz, Spain ; Department of Pharmacology, University of Michigan, Ann Arbor, USA
Gómez Oliva, Ricardo  ;  Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Division of Physiology, University of Cadiz, Cadiz, Spain ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain
Martínez-Gómez, Nora;  Department of Physiology, University of Seville, Seville, Spain
Domínguez-García, Samuel;  Division of Physiology, University of Cadiz, Cadiz, Spain ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain ; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
García-Cózar, Francisco;  Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain ; Division of Immunology, University of Cadiz, Cadiz, Spain
Muñoz-Miranda, Juan Pedro;  Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain ; Division of Immunology, University of Cadiz, Cadiz, Spain
Hernández-Galán, Rosario;  Department of Organic Chemistry, University of Cadiz, Cadiz, Spain ; Biomolecules Institute (INBIO), Puerto Real, Cadiz, Spain
Carrascal, Livia;  Department of Physiology, University of Seville, Seville, Spain ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain
Castro, Carmen ;  Division of Physiology, University of Cadiz, Cadiz, Spain. carmen.castro@uca.es ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain. carmen.castro@uca.es
Nunez-Abades, Pedro;  Department of Physiology, University of Seville, Seville, Spain. pnunez@us.es ; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain. pnunez@us.es
Language :
English
Title :
The subventricular zone neurogenic niche provides adult born functional neurons to repair cortical brain injuries in response to diterpenoid therapy.
Publication date :
05 January 2025
Journal title :
Stem Cell Research and Therapy
eISSN :
1757-6512
Publisher :
BioMed Central Ltd, England
Volume :
16
Issue :
1
Pages :
1
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
AEI - Agencia Estatal de Investigación
UCA - Universidad de Cádiz
Funding text :
Funding for open access publishing: Universidad de C\u00E1diz/CBUA. This publication is part of the I\u2009+\u2009D\u2009+\u2009i (PID2022-142418OB-C21) grant funded by MICIU/AEI/ https://doi.org/10.13039/501100011033 and by ERDF/UE.Funding for open access publishing: Universidad de C\u00E1diz/CBUA
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