Zebrafish as a translational regeneration model to study the activation of neural stem cells and role of their environment

Abstract

The review is an overview of the current knowledge of neuronal regeneration properties in mammals and fish. The ability to regenerate the damaged parts of the nervous tissue has been demonstrated in all vertebrates. Notably, fish and amphibians have the highest capacity for neurogenesis, whereas reptiles and birds are able to only regenerate specific regions of the brain, while mammals have reduced capacity for neurogenesis. Zebrafish (Danio rerio) is a promising model of study because lesions in the brain or complete cross-section of the spinal cord are followed by an effective neuro-regeneration that successfully restores the motor function. In the brain and the spinal cord of zebrafish, stem cell activity is always able to re-activate the molecular programs required for central nervous system regeneration. In mammals, traumatic brain injuries are followed by reduced neurogenesis and poor axonal regeneration, often insufficient to functionally restore the nervous tissue, while spinal injuries are not repaired at all. The environment that surrounds the stem cell niche constituted by connective tissue and stimulating factors, including pro-inflammation molecules, seems to be a determinant in triggering stem cell proliferation and/or the trans-differentiation of connective elements (mainly fibroblasts). Investigating and comparing the neuronal regeneration in zebrafish and mammals may lead to a better understanding of the mechanisms behind neurogenesis, and the failure of the regenerative response in mammals, first of all, the role of inflammation, considered the main inhibitor of the neuronal regeneration.

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

“…This finding was different from the findings from rodents where a single high dose of KA produces full-blown seizure (Demars et al., 2018). This might be due to the virtue (ability of excellence or performance) of zebrafish and its regenerative property which regenerates the damaged neurons and makes the fish less sensitive (Ceci et al., 2018). These findings implicate that a single dose of KA (3 mg/kg) lack (reduced in sensitivity or less sensitive) produce long term sensitivity in zebrafish for epileptic seizures.…”

Remote ischemic conditioning improves outcome independent of anesthetic effects following shockwave-induced traumatic brain injury

“…There are notable differences regarding the reparative potential of the zebrafish brain compared to that of mammals. (Ceci et al, 2018; Kizil et al, 2012) Studies in both larvae and adult zebrafish demonstrate a remarkable ability for regeneration of damaged neural tissues following penetrating mechanical insult (Cacialli et al, 2018; Herzog et al, 2019; Shimizu et al, 2018) which is in obvious contrast to the mammalian capacity for neural regeneration of injured tissues. Our model of pHIFU-induced brain injury does not involve obvious penetrating trauma to the brain or overt cell loss as induced in these other studies.…”

Hedgehog Signaling Regulates Neurogenesis in the Larval and Adult Zebrafish Hypothalamus

“…Cell-cell signaling systems that regulate nervous system development such as the Notch, Fibroblast Growth Factor (FGF), Wnt, Hedgehog (Hh), and Bone Morphogenetic (BMP) signaling pathways play a key role in controlling adult neurogenesis (Kizil et al, 2012;Petrova and Joyner, 2014;Anand and Mondal, 2017;Obernier and Alvarez-Buylla, 2019). Heterogeneity in both neural stem cell populations and in cell-cell signaling systems helps control the range of differentiated cell types that are produced in stem cell niches (Marz et al, 2010;Chaker et al, 2016;Lim and Alvarez-Buylla, 2016;Ceci et al, 2018). Determining how this heterogeneity contributes to brain growth and adult neurogenesis remains a major challenge in the field.…”