Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?

Geribaldi-Doldán, Noelia; Carrascal, Livia; Pérez-García, Patricia; Oliva-Montero, José María; Pardillo-Díaz, Ricardo; Domínguez-García, Samuel; Bernal‐Utrera, Carlos; Gómez-Oliva, Ricardo; Martínez-Ortega, Sergio; Escolano, Cristina Verástegui; Nuñez-Abades, Pedro; Castro, Carmen

doi:10.3390/ijms24076587

Cited by 7 publications

(6 citation statements)

References 282 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain injuries of different origins such as traumatic, ischemic or neurodegenerative stimulate neurogenesis in the SVZ resulting in a higher number of newly generated neuroblasts that attempt to migrate toward the injury [ 53 ] but do not reach the perilesional area [ 16 , 19 ] not contributing to neuronal replacement and to the regeneration of the injured region. Failure of neuroblasts to migrate toward the injury has been reported to be a consequence of the presence or absence of signaling molecules that affect neuroblast migration [ 33 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries

Gómez-Oliva,

Geribaldi-Doldán,

Domínguez-García

et al. 2023

J Transl Med

Self Cite

View full text Add to dashboard Cite

Background Neurogenesis is stimulated in the subventricular zone (SVZ) of mice with cortical brain injuries. In most of these injuries, newly generated neuroblasts attempt to migrate toward the injury, accumulating within the corpus callosum not reaching the perilesional area. Methods We use a murine model of mechanical cortical brain injury, in which we perform unilateral cortical injuries in the primary motor cortex of adult male mice. We study neurogenesis in the SVZ and perilesional area at 7 and 14 dpi as well as the expression and concentration of the signaling molecule transforming growth factor alpha (TGF-α) and its receptor the epidermal growth factor (EGFR). We use the EGFR inhibitor Afatinib to promote neurogenesis in brain injuries. Results We show that microglial cells that emerge within the injured area and the SVZ in response to the injury express high levels of TGF-α leading to elevated concentrations of TGF-α in the cerebrospinal fluid. Thus, the number of neuroblasts in the SVZ increases in response to the injury, a large number of these neuroblasts remain immature and proliferate expressing the epidermal growth factor receptor (EGFR) and the proliferation marker Ki67. Restraining TGF-α release with a classical protein kinase C inhibitor reduces the number of these proliferative EGFR+ immature neuroblasts in the SVZ. In accordance, the inhibition of the TGF-α receptor, EGFR promotes migration of neuroblasts toward the injury leading to an elevated number of neuroblasts within the perilesional area. Conclusions Our results indicate that in response to an injury, microglial cells activated within the injury and the SVZ release TGF-α, activating the EGFR present in the neuroblasts membrane inducing their proliferation, delaying maturation and negatively regulating migration. The inactivation of this signaling pathway stimulates neuroblast migration toward the injury and enhances the quantity of neuroblasts within the injured area. These results suggest that these proteins may be used as target molecules to regenerate brain injuries.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries

Gómez-Oliva,

Geribaldi-Doldán,

Domínguez-García

et al. 2023

J Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…NSCs can expand long basal processes that envelop the vessels by expressing laminins and integrins typical of the SVZ [ 146 ]. In addition, vasculature is related to the migration of NSCs and its progeny, serving as support scaffolds [ 31 , 147 ]. Related to this microenvironment close to the sanguine vessels, non-neurogenic functions can be attributed to NSCs, but taking into account neuromodulatory and neuroprotective functions.…”

Section: Neurogenesis In the Subventricular Zonementioning

confidence: 99%

“…In addition, OB neurogenesis in mice has been described as an additional process throughout life [ 149 , 150 ], whereas, in adult humans, researchers were unable to find neurogenesis in the OB, nor the addition of new neuroblasts generated from the SVZ to the OB [ 2 , 151 ]. However, neuroblasts from the SVZ can migrate to other brain regions in the human brain, such as the basal ganglia and the cerebral cortex, mostly under pathological conditions [ 31 , 39 , 152 ].…”

Section: Neurogenesis In the Subventricular Zonementioning

confidence: 99%

“…Recently, using single-cell transcriptome analyes, specific molecular components were revealed to have association owing to ageing, specifically the tyrosine-protein kinase Abl1 [ 30 ]. Some studies have investigated the migratory processes of various pathology-related regions, pinpointing specific molecules that determine the direction and type of migration of NSCs and their progeny [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exploring the Intricacies of Neurogenic Niches: Unraveling the Anatomy and Neural Microenvironments

Sánchez-Gomar,

Geribaldi-Doldán,

Santos-Rosendo

et al. 2024

Biomolecules

Self Cite

View full text Add to dashboard Cite

Neurogenesis is the process of forming new neurons from neural stem cells (NSCs). In adults, this process takes place in specific areas of the brain, known as neurogenic niches. These regions have unique anatomical features that have been studied in animal models and in the human brain; however, there are differences between these models that need to be addressed. The most studied areas are the subventricular zone, the lateral and latero-dorsal walls of the lateral ventricles, and the dentate gyrus of the hippocampus (Hp), which are known as the canonical areas. Other, less-studied niches, such as the hypothalamus, the cerebellum, and the amygdala, are known as non-canonical areas. Anatomy occupies a relevant place in adult neurogenesis, in which the tissue architecture and cellular location are necessities for the interaction and release of diverse molecules that allow this phenomenon. The cell arrangement within the niche and the location of the niche itself are of particular relevance to the state in which the NSCs are found. Consequently, the majority of previous discoveries have been related to pathology. While many studies are based on animal models, discoveries related to neurogenesis in humans have also been made; however, in this case, opinions vary, leading to extensive controversy in recent years. In this review, we address the anatomical characteristics of the different brain regions to better understand their relationships within neurogenesis.

show abstract

“…The potential proliferation of precursor stem cells provides the mature brain with flexibility and self-renewal through neurogenesis, which occurs in response to external stimuli and damage [97,98]. It has been shown that in the ischemia-tolerant brain, the proliferation of precursor cells increases after focal ischemia and preconditioning [99,100].…”

Section: Proliferative and Synthetic Activitymentioning

confidence: 99%

Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia

Tregub,

Kulikov,

Ibrahimli

et al. 2024

IJMS

View full text Add to dashboard Cite

The review introduces the stages of formation and experimental confirmation of the hypothesis regarding the mutual potentiation of neuroprotective effects of hypoxia and hypercapnia during their combined influence (hypercapnic hypoxia). The main focus is on the mechanisms and signaling pathways involved in the formation of ischemic tolerance in the brain during intermittent hypercapnic hypoxia. Importantly, the combined effect of hypoxia and hypercapnia exerts a more pronounced neuroprotective effect compared to their separate application. Some signaling systems are associated with the predominance of the hypoxic stimulus (HIF-1α, A1 receptors), while others (NF-κB, antioxidant activity, inhibition of apoptosis, maintenance of selective blood–brain barrier permeability) are mainly modulated by hypercapnia. Most of the molecular and cellular mechanisms involved in the formation of brain tolerance to ischemia are due to the contribution of both excess carbon dioxide and oxygen deficiency (ATP-dependent potassium channels, chaperones, endoplasmic reticulum stress, mitochondrial metabolism reprogramming). Overall, experimental studies indicate the dominance of hypercapnia in the neuroprotective effect of its combined action with hypoxia. Recent clinical studies have demonstrated the effectiveness of hypercapnic–hypoxic training in the treatment of childhood cerebral palsy and diabetic polyneuropathy in children. Combining hypercapnic hypoxia with pharmacological modulators of neuro/cardio/cytoprotection signaling pathways is likely to be promising for translating experimental research into clinical medicine.

show abstract

Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?

Cited by 7 publications

References 282 publications

Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries

Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries

Exploring the Intricacies of Neurogenic Niches: Unraveling the Anatomy and Neural Microenvironments

Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia

Contact Info

Product

Resources

About