The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical...The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.展开更多
Time windows for postnatal changes in morphology and membrane excitability of genioglossal(GG) and oculomotor(OCM) motoneurons(MNs) are yet to be fully described. Analysis of data on brain slices in vitro of the 2 pop...Time windows for postnatal changes in morphology and membrane excitability of genioglossal(GG) and oculomotor(OCM) motoneurons(MNs) are yet to be fully described. Analysis of data on brain slices in vitro of the 2 populations of MNs point to a well-defined developmental program that progresses with common age-related changes characterized by:(1) increase of dendritic surface along with length and reshaping of dendritic tree complexity;(2) disappearance of gap junctions early in development;(3) decrease of membrane passive properties, such as input resistance and time constant, together with an increase in the number of cells displaying sag, and modifications in rheobase;(4) action potential shortening and afterhyperpolarization; and(5) an increase in gain and maximum firing frequency. These modifications take place at different time windows for each motoneuronal population. In GG MNs, active membrane properties change mainly during the first postnatal week, passive membrane properties in the second week, and dendritic increasing length and size in the third week of development. In OCM MNs, changes in passive membrane properties and growth of dendritic size take place during the first postnatal week, while active membrane properties and rheobase change during the second and third weeks of development. The sequential order of changes is inverted between active and passive membrane properties, and growth in size does not temporally coincide for both motoneuron populations. These findings are discussed on the basis of environmental cues related to maturation of the respiratory and OCM systems.展开更多
基金supported by the I+D+i(PID2022-142418OB-C21)grant funded by MICIU/AEI/10.13039/501100011033 and by ERDF/UE.
文摘The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.
文摘Time windows for postnatal changes in morphology and membrane excitability of genioglossal(GG) and oculomotor(OCM) motoneurons(MNs) are yet to be fully described. Analysis of data on brain slices in vitro of the 2 populations of MNs point to a well-defined developmental program that progresses with common age-related changes characterized by:(1) increase of dendritic surface along with length and reshaping of dendritic tree complexity;(2) disappearance of gap junctions early in development;(3) decrease of membrane passive properties, such as input resistance and time constant, together with an increase in the number of cells displaying sag, and modifications in rheobase;(4) action potential shortening and afterhyperpolarization; and(5) an increase in gain and maximum firing frequency. These modifications take place at different time windows for each motoneuronal population. In GG MNs, active membrane properties change mainly during the first postnatal week, passive membrane properties in the second week, and dendritic increasing length and size in the third week of development. In OCM MNs, changes in passive membrane properties and growth of dendritic size take place during the first postnatal week, while active membrane properties and rheobase change during the second and third weeks of development. The sequential order of changes is inverted between active and passive membrane properties, and growth in size does not temporally coincide for both motoneuron populations. These findings are discussed on the basis of environmental cues related to maturation of the respiratory and OCM systems.
