Estrogenic regulation of claudin 5 and tight junction protein 1 gene expression in zebrafish: A role on blood-brain barrier?

The blood-brain barrier (BBB) is a physical interface between the blood and the brain parenchyma, playing key roles in brain homeostasis. In mammals, the BBB is established thanks to tight junctions between cerebral endothelial cells, involving claudin, occludin, and zonula occludens proteins. Estrogens have been documented to modulate BBB permeability.

Interference with zinc homeostasis and oxidative stress induction as probable mechanisms for cadmium-induced embryo-toxicity in zebrafish.

The present study was conducted to provide new insights into the mechanisms that may be responsible for cadmium (Cd)-induced toxicity in zebrafish larvae as well as the role of the trace element zinc (Zn) in reversing Cd harmful effects. For this purpose, zebrafish eggs were exposed to Cd or/and Zn for 96 h. The effects on morphological aspect; mortality rate; Cd, Zn, and metallothionein (MT) levels; oxidative stress biomarkers; as well as molecular expression of some genes involved in Zn metabolism (Zn-MT, ZIP10, and ZnT1) and in antioxidant defense system (Cu/Zn-SOD, CAT and GPx) were examined.

Neurodevelopmental effects of natural and synthetic ligands of estrogen and progesterone receptors in zebrafish eleutheroembryos.

Natural and synthetic estrogens and progestins are widely used in human and veterinary medicine and are detected in waste and surface waters. Our previous studies have clearly shown that a number of these substances targets the brain to induce the estrogen-regulated brain aromatase expression but the consequences on brain development remain virtually unexplored. The aim of the present study was therefore to investigate the effect of estradiol (E2), progesterone (P4) and norethindrone (NOR), a 19-nortestosterone progestin, on zebrafish larval neurogenesis.

Glyphosate and glyphosate-based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behaviour and microbiome.

Glyphosate is found in a large array of non-selective herbicides such as Roundup® (Monsanto, Creve Coeur, MO, USA) and is by far the most widely used herbicide. Recent work in rodent models suggests that glyphosate-based herbicides during development can affect neuronal communication and result in altered behaviours, albeit through undefined mechanisms of action. To our knowledge, no study has investigated the effects glyphosate or its formulation in herbicide on maternal behaviour and physiology.

Neuronal expression of brain derived neurotrophic factor in the injured telencephalon of adult zebrafish.

The reparative ability of the central nervous system varies widely in the animal kingdom. In the mammalian brain, the regenerative mechanisms are very limited and newly formed neurons do not survive longer, probably due to a non-suitable local environment. On the opposite, fish can repair the brain after injury, with fast and complete recovery of damaged area.

Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc.

The present study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, as well as the potential protective role of Zn against Cd-induced toxicity. For this purpose, the effects on transcriptional activation of the estrogen receptors (ERs), aromatase B (Aro-B) protein expression and molecular expression of related genes were examined in vivo using wild-type and transgenic zebrafish embryos. For in vitro studies, an ER-negative glial cell line (U251MG) transfected with different zebrafish ER subtypes (ERα, ERβ1 and ERβ2) was also used.

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

Estrogens are known as steroid hormones affecting the brain in many different ways and a wealth of data now document effects on neurogenesis. Estrogens are provided by the periphery but can also be locally produced within the brain itself due to local aromatization of circulating androgens. Adult neurogenesis is described in all vertebrate species examined so far, but comparative investigations have brought to light differences between vertebrate groups.

Relationships between radial glial progenitors and 5-HT neurons in the paraventricular organ of adult zebrafish - potential effects of serotonin on adult neurogenesis.

In non-mammalian vertebrates, serotonin (5-HT)-producing neurons exist in the paraventricular organ (PVO), a diencephalic structure containing cerebrospinal fluid (CSF)-contacting neurons exhibiting 5-HT or dopamine (DA) immunoreactivity. Because the brain of the adult teleost is known for its neurogenic activity supported, for a large part, by radial glial progenitors, this study addresses the origin of newborn 5-HT neurons in the hypothalamus of adult zebrafish. In this species, the PVO exhibits numerous radial glial cells (RGCs) whose somata are located at a certain distance from the ventricle.

Expression of aromatase in radial glial cells in the brain of the Japanese eel provides insight into the evolution of the cyp191a gene in Actinopterygians.

The cyp19a1 gene that encodes aromatase, the only enzyme permitting conversion of C19 aromatizable androgens into estrogens, is present as a single copy in the genome of most vertebrate species, except in teleosts in which it has been duplicated. This study aimed at investigating the brain expression of a cyp19a1 gene expressed in both gonad and brain of Japanese eel, a basal teleost. By means of immunohistochemistry and in situ hybridization, we show that cyp19a1 is expressed only in radial glial cells of the brain and in pituitary cells.

Nuclear progesterone receptors are up-regulated by estrogens in neurons and radial glial progenitors in the brain of zebrafish.

In rodents, there is increasing evidence that nuclear progesterone receptors are transiently expressed in many regions of the developing brain, notably outside the hypothalamus. This suggests that progesterone and/or its metabolites could be involved in functions not related to reproduction, particularly in neurodevelopment. In this context, the adult fish brain is of particular interest, as it exhibits constant growth and high neurogenic activity that is supported by radial glia progenitors.

Cxcr4 and Cxcl12 expression in radial glial cells of the brain of adult zebrafish.

Unlike that of mammals, the brain of adult teleost fish exhibits an intense and widespread neurogenic activity as a result of the persistence of radial glial cells acting as neural progenitors throughout life. Because chemokines, notably CXCL12, and their receptors, such as CXCR4, play key roles in mammalian embryonic neurogenesis, we investigated Cxcr4 and Cxcl12 expressions in the brain of adult zebrafish and their potential relationships with cell proliferation. Cxcr4 expression was found to be restricted to radial glial cells in the adult zebrafish, where it is co-expressed with established radial glial cell markers, such as brain lipid-binding protein (Blbp) or the estrogen-synthesizing enzyme aromatase B (Cyp19a1b).

Sexual dimorphism in the brain aromatase expression and activity, and in the central expression of other steroidogenic enzymes during the period of sex differentiation in monosex rainbow trout populations.

Using genetic monosex male and female rainbow trout populations, the potential sex differences in the central expression of estrogen receptors (esr1, esr2a, esr2b), brain aromatase (cyp19a1b) and some other steroidogenic enzymes was studied over the period of sex differentiation (from 35 to 63 dpf: days post-fertilization) using quantitative polymerase chain reaction (q-PCR). In addition, aromatase activity was evaluated during this period. The results indicated that brain aromatase (cyp19a1b) expression and activity showed a clear and significant sexually dimorphic pattern with higher levels in male brain between 35 and 53 dpf before the time of gonad morphological differentiation.

Progenitor radial cells and neurogenesis in pejerrey fish forebrain.

The central nervous system of adult teleost fish is peculiar because of the following features: (1) the persistence of radial glial cells, (2) an important neurogenic activity and (3) a high aromatase expression by radial cells. In this study, the proliferative zones of the forebrain were described using bromodeoxyuridine (BrdU) treatment in the brain of the pejerrey, an Acanthopterygian teleost fish. These cells were shown to have morphological and immunoreactive characteristics of radial cells and to express aromatase.

Androgens upregulate cyp19a1b (aromatase B) gene expression in the brain of zebrafish (Danio rerio) through estrogen receptors.

The brain of teleosts is known for its strong aromatase expression, exhibiting unique features compared with other vertebrates. Among these features is the high sensitivity of aromatase B (the product of cyp19a1b) to estrogens. This effect involves the binding of estrogen receptors on an estrogen-responsive element (ERE) of the cyp19a1b promoter.

A cyp19a1b-gfp (aromatase B) transgenic zebrafish line that expresses GFP in radial glial cells.

Aromatase is an enzyme that catalyzes the synthesis of estrogen in gonads and brain. Teleost fish express aromatase (AroB) strongly in the brain facilitating its detailed examination. To understand the function of AroB in the brain, we generated transgenic zebrafish that expresses green fluorescent protein (GFP) driven by the brain aromatase cyp19a1b promoter.

Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations.

Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, alpha and beta, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads.

COUP-TFI modulates estrogen signaling and influences proliferation, survival and migration of breast cancer cells.

We previously showed that COUP-TFI interacts with the Estrogen Receptor alpha (ER alpha) to recruit Extracellular signal Regulated Kinases (ERKs) in an Estradiol (E2)-independent manner, resulting in an enhancement of ER alpha transcriptional activity. However, the involvement of COUP-TFI in physiologically relevant functions of ER alpha, such as the mitogenic activity that E2 has on breast cancer cells, remains poorly understood. Here, we first showed that the amounts of COUP-TFI protein are higher in dedifferentiated mammary cell lines (MDA-MB-231) and tumor breast cells as compared to the differentiated MCF-7 cell line and normal breast cells.

Identification of aromatase-positive radial glial cells as progenitor cells in the ventricular layer of the forebrain in zebrafish.

Compared with other vertebrates, the brain of adult teleost fish exhibits two unique features: it exhibits unusually high neurogenic activity and strongly expresses aromatase, a key enzyme that converts aromatizable androgens into estrogens. Until now, these two features, high neurogenic and aromatase activities, have never been related to each other. Recently, it was shown that aromatase is expressed in radial glial cells of the forebrain and not in neurons.

Relationships between aromatase and estrogen receptors in the brain of teleost fish.

Teleost fish are known for exhibiting a high aromatase activity mainly due to the expression of the cyp19b gene, encoding aromatase B (AroB). Recent studies based on both in situ hybridization and immunohistochemistry have demonstrated in three different species that this activity is restricted to radial glial cells. In agreement with measurements of aromatase activity, such aromatase-expressing cells are more abundant in the telencephalon, preoptic area, and mediobasal hypothalamus, although positive cells are also found in the midbrain and hindbrain.