The subventricular zone neurogenic niche provides adult born functional neurons to repair cortical brain injuries in response to diterpenoid therapy. - 2025
[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.
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.
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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