Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals

In contrast to mammals, the adult zebrafish brain shows neurogenic activity in a multitude of niches present in almost all brain subdivisions. Irrespectively, constitutive neurogenesis in the adult zebrafish and mouse telencephalon share many similarities at the cellular and molecular level. However, upon injury during tissue repair, the situation is entirely different. In zebrafish, inflammation caused by traumatic brain injury or by induced neurodegeneration initiates specific and distinct neurogenic programs that, in combination with signaling pathways implicated in constitutive neurogenesis, quickly, and efficiently overcome the loss of neurons. In the mouse brain, injury-induced inflammation promotes gliosis leading to glial scar formation and inhibition of regeneration. A better understanding of the regenerative mechanisms occurring in the zebrafish brain could help to develop new therapies to combat the debilitating consequences of brain injury, stroke, and neurodegeneration. The aim of this review is to compare the properties of neural progenitors and the signaling pathways, which control adult neurogenesis and regeneration in the zebrafish and mammalian telencephalon

Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals after Injury

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity, and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia, and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals, one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity

Stem cells and the circadian clock

The circadian timing system is a complex biological network of interacting circadian clocks that regulates 24 h rhythms of behavioral and physiological processes. One intriguing observation is that stem cell homeostasis is subject to circadian clock regulation. Rhythmic oscillations have been observed in a variety of embryonic and adult stem cell dependent processes, such as hematopoietic progenitor cell migration, the hair follicle cycle, bone remodeling, regenerative myogenesis and neurogenesis. This review aims to discuss the nature of the circadian clock in embryonic stem cells and how it changes during differentiation. Furthermore, it will examine how the circadian clock contributes to adult stem cell function in different tissues of the body with an emphasis on the brain and adult neurogenesis

Neuron-Radial Glial Cell Communication via BMP/Id1 Signaling Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon

The central nervous system of adult zebrafish displays an extraordinary neurogenic and regenerative capacity. In the zebrafish adult brain, this regenerative capacity relies on neural stem cells (NSCs) and the careful management of the NSC pool. However, the mechanisms controlling NSC pool maintenance are not yet fully understood. Recently, Bone Morphogenetic Proteins (BMPs) and their downstream effector Id1 (Inhibitor of differentiation 1) were suggested to act as key players in NSC maintenance under constitutive and regenerative conditions. Here, we further investigated the role of BMP/Id1 signaling in these processes, using different genetic and pharmacological approaches. Our data show that BMPs are mainly expressed by neurons in the adult telencephalon, while id1 is expressed in NSCs, suggesting a neuron-NSC communication via the BMP/Id1 signaling axis. Furthermore, manipulation of BMP signaling by conditionally inducing or repressing BMP signaling via heat-shock, lead to an increase or a decrease of id1 expression in the NSCs, respectively. Induction of id1 was followed by an increase in the number of quiescent NSCs, while knocking down id1 expression caused an increase in NSC proliferation. In agreement, genetic ablation of id1 function lead to increased proliferation of NSCs, followed by depletion of the stem cell pool with concomitant failure to heal injuries in repeatedly injured mutant telencephala. Moreover, pharmacological inhibition of BMP and Notch signaling suggests that the two signaling systems cooperate and converge onto the transcriptional regulator her4.1. Interestingly, brain injury lead to a depletion of NSCs in animals lacking BMP/Id1 signaling despite an intact Notch pathway. Taken together, our data demonstrate how neurons feedback on NSC proliferation and that BMP1/Id1 signaling acts as a safeguard of the NSC pool under regenerative conditions

HDL biodistribution and brain receptors in zebrafish, using HDLs as vectors for targeting endothelial cells and neural progenitors

High density lipoproteins (HDLs) display pleiotropic functions such as anti-inflammatory, antioxidant, anti-protease, and anti-apoptotic properties. These effects are mediated by four main receptors: SCARB1 (SR-BI), ABCA1, ABCG1, and CD36. Recently, HDLs have emerged for their potential involvement in brain functions, considering their epidemiological links with cognition, depression, and brain plasticity. However, their role in the brain is not well understood. Given that the zebrafish is a well-recognized model for studying brain plasticity, metabolic disorders, and apolipoproteins, it could represent a good model for investigating the role of HDLs in brain homeostasis. By analyzing RNA sequencing data sets and performing in situ hybridization, we demonstrated the wide expression of scarb1, abca1a, abca1b, abcg1, and cd36 in the brain of adult zebrafish. Scarb1 gene expression was detected in neural stem cells (NSCs), suggesting a possible role of HDLs in NSC activity. Accordingly, intracerebroventricular injection of HDLs leads to their uptake by NSCs without modulating their proliferation. Next, we studied the biodistribution of HDLs in the zebrafish body. In homeostatic conditions, intraperitoneal injection of HDLs led to their accumulation in the liver, kidneys, and cerebral endothelial cells in zebrafish, similar to that observed in mice. After telencephalic injury, HDLs were diffused within the damaged parenchyma and were taken up by ventricular cells, including NSCs. However, they failed to modulate the recruitment of microglia cells at the injury site and the injury-induced proliferation of NSCs. In conclusion, our results clearly show a functional HDL uptake process involving several receptors that may impact brain homeostasis and suggest the use of HDLs as delivery vectors to target NSCs for drug delivery to boost their neurogenic activity

Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders

Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish

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Aromatase in the brain of teleost fish: expression, regulation and putative functions.

International audienceUnlike that of mammals, the brain of teleost fish exhibits an intense aromatase activity due to the strong expression of one of two aromatase genes (aromatase A or cyp19a1a and aromatase B or cyp19a1b) that arose from a gene duplication event. In situ hybridization, immunohistochemistry and expression of GFP (green fluorescent protein) in transgenic tg(cyp19a1b-GFP) fish demonstrate that aromatase B is only expressed in radial glial cells (RGC) of adult fish. These cells persist throughout life and act as progenitors in the brain of both developing and adult fish. Although aromatase B-positive radial glial cells are most abundant in the preoptic area and the hypothalamus, they are observed throughout the entire central nervous system and spinal cord. In agreement with the fact that brain aromatase activity is correlated to sex steroid levels, the high expression of cyp19a1b is due to an auto-regulatory loop through which estrogens and aromatizable androgens up-regulate aromatase expression. This mechanism involves estrogen receptor binding on an estrogen response element located on the cyp19a1b promoter. Cell specificity is achieved by a mandatory cooperation between estrogen receptors and unidentified glial factors. Given the emerging roles of estrogens in neurogenesis, the unique feature of the adult fish brain suggests that, in addition to classical functions on brain sexual differentiation and sexual behaviour, aromatase expression in radial glial cells could be part of the mechanisms authorizing the maintenance of a high proliferative activity in the brain of fish