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Estrogens affect brain development of vertebrates, not only by impacting activity and morphology of existing circuits, but also by modulating embryonic and adult neurogenesis. The issue is complex as estrogens can not only originate from peripheral tissues, but also be locally produced within the brain itself due to local aromatization of androgens. In this respect, teleost fishes are quite unique because aromatase is expressed exclusively in radial glial cells, which represent pluripotent cells in the brain of all vertebrates. Expression of aromatase in the brain of fish is also strongly stimulated by estrogens and some androgens. This creates a very intriguing positive auto-regulatory loop leading to dramatic aromatase expression in sexually mature fish with elevated levels of circulating steroids. Looking at the effects of estrogens or anti-estrogens in the brain of adult zebrafish showed that estrogens inhibit rather than stimulate cell proliferation and newborn cell migration. The functional meaning of these observations is still unclear, but these data suggest that the brain of fish is experiencing constant remodeling under the influence of circulating steroids and brain-derived neurosteroids, possibly permitting a diversification of sexual strategies, notably hermaphroditism. Recent data in frogs indicate that aromatase expression is limited to neurons and do not concern radial glial cells. Thus, until now, there is no other example of vertebrates in which radial progenitors express aromatase. This raises the question of when and why these new features were gained and what are their adaptive benefits. This article is part of a Special Issue entitled: Nuclear receptors in animal development., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Glycine and γ-aminobutyric acid (GABA) are the main inhibitory neurotransmitters in the central nervous system (CNS) of vertebrates. Studies on the distribution of glycinergic neurons and fibers have been carried out mainly in rodents and lampreys. With the aim of discovering more about the early evolution of this system in vertebrates, we analyzed the distribution of glycine-immunoreactive (Gly-ir) neurons and fibers in the CNS of a basal ray-finned fish, the Siberian sturgeon (Chondrostei, Acipenseriformes), by use of immunohistochemical techniques. We also compared the distribution of glycine and GABA by the use of double-immunofluorescence techniques and confocal microscopy. Our results revealed the presence of Gly-ir cells in different regions of the CNS, such as olfactory bulbs, preoptic area, hypothalamus, thalamus, pretectum, optic tectum, tegmentum and rostral spinal cord, although most of the Gly-ir cells and the most intensely immunoreactive cells were located in the rhombencephalon, mainly in the octavolateral area and reticular formation. In addition, coronet cells of the basal hypothalamus and saccus vasculosus were Gly-ir. Glycinergic fibers coursed along most brain regions and were more abundant in the thalamus, hypothalamus, optic tectum, tegmentum, isthmic region, and basal rhombencephalon. The Mauthner cell perikaryon was richly innervated by Gly-ir boutons, as reported for teleosts. With regard to the colocalization of glycine and GABA, double-immunoreactive cells were located mainly in the rhombencephalon. The results enable us to conclude that the distribution of glycine in the sturgeon brain is more similar to that observed in lampreys than that observed in mammals., (Copyright © 2011 Wiley-Liss, Inc.)

Somatostatin (SOM) is a neuropeptide that is widely distributed in the central nervous system of vertebrates. Two isoforms of somatostatin (SS1 and SS2) have been characterized in sturgeon and in situ hybridisation studies in the sturgeon brain have demonstrated that mRNAs of the two somatostatin precursors (PSS1 and PSS2) are differentially expressed in neurons [Trabucchi, M., Tostivint, H., Lihrmann, I., Sollars, C., Vallarino, M., Dores, R.M., Vaudry, H., 2002. Polygenic expression of somatostatin in the sturgeon Acipenser transmontanus: molecular cloning and distribution of the mRNAs encoding two somatostatin precursors. J. Comp. Neurol. 443, 332-345.]. However, neither the morphology of somatostatinergic neurons nor the patterns of innervation have yet been characterized. To gain further insight into the evolution of this system in primitive bony fishes, we studied the distribution of somatostatin-immunoreactive (SOM-ir) cells and fibres in the brain of the Siberian sturgeon (Acipenser baeri). Most SOM-ir cells were found in the preoptic area and hypothalamus and abundant SOM-ir fibres coursed along the hypothalamic floor towards the median eminence, suggesting a hypophysiotrophic role for SOM in sturgeon. In addition, SOM-ir cells and fibres were observed in extrahypothalamic regions such as the telencephalon thalamus, rhombencephalon and spinal cord, which also suggests neuromodulatory and/or neurotransmitter functions for this peptide. Overall there was a good correlation between the distribution of SOM-ir neurons throughout the brain of A. baeri and that of PSS1 mRNA in Acipenser transmontanus. Comparative analysis of the results with those obtained in other groups of fishes and tetrapods indicates that widespread distribution of this peptide in the brain is shared by early vertebrate lines and that the general organization of the somatostatinergic systems has been well-conserved during evolution.

In contrast to other vertebrates, in which the adult brain shows limited adult neurogenesis, teleost fishes exhibit an unparalleled capacity to generate new neurons as adults, suggesting that their brains present a highly permissive environment for the maintenance and proliferation of adult progenitors. Here, we examine the hypothesis that one of the factors permitting establishment of this favourable environment is estradiol. Indeed, recent data showed that radial glial cells strongly expressed one of two aromatase duplicated genes. Aromatase is the estrogen-synthesizing enzyme and this observation is of great interest, given that radial glial cells are progenitor cells capable of generating new neurons. Given the well-documented roles of estrogens on cell fate, and notably on cell proliferation, these data suggest that estradiol could be involved in maintaining and/or activating these progenitors. Examination of recent data in birds and mammals suggests that the situation in fish could well be an exaggeration of a more general mechanism implicating estrogens in neurogenesis. Indeed, there is accumulating evidence that estrogens are involved in embryonic, adult or reparative neurogenesis in other vertebrates, notably in mammals.

Galanin is a 29-amino acid peptide widely distributed in the central nervous system of vertebrates. The organization of galaninergic systems is well known in teleosts, the most advanced actinopterygians, but no data are available on primitive bony fish. To extend the evolutionary analysis of galaninergic systems we studied the distribution of galanin-like immunoreactive (GAL-ir) cells and fibers in the sturgeon brain, since chondrosteans are among the most primitive extant actinopterygians. Double-immunolabeling experiments were performed to compare the distribution of galanin with that of neurophysin, tyrosine hydroxylase, and serotonin. Numerous GAL-ir cells of cerebrospinal fluid-contacting (CSF-C) type were found in the ventral telencephalon, preoptic area, and in the tuberal and caudal hypothalamus. The distribution of GAL-ir elements in the sturgeon brain shows many similarities to that observed in other vertebrates, but also important differences, such as the abundance of GAL-ir CSF-C cells, which appear to be a primitive characteristic. GAL-ir neurons observed in the sturgeon telencephalic hemispheres perhaps represent the basic organization of common ancestors of bony fishes and tetrapods. In the preoptic-hypophyseal system, GAL-ir cells appeared to be related not only with neurophysin-expressing neurons (in the tuberal hypothalamus) but also with serotoninergic and catecholamines-synthesizing neurons (in preoptic and tuberal nuclei). Numerous GAL-ir fibers were observed in the median eminence and neural lobe of the hypophysis, indicating that galanin may play a role in the modulation of hypophyseal secretion. GAL-ir neurons were absent from the sturgeon brainstem, suggesting that their presence in other vertebrates could represent an evolutionary recent acquisition., ((c) 2005 Wiley-Liss, Inc.)

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. Comparative distribution of AroB and estrogen receptor (ERalpha, ERbeta1, and ERbeta2) expression indicates that the preoptic region and hypothalamus are major target for locally produced estradiol (E2) which is likely involved in controlling expression of genes implicated in neuroendocrine regulations. However, AroB and ER have never been reported to be co-expressed in the same cells which is intriguing given that, at least in some species, AroB is strongly up-regulated by E2 itself in agreement with the presence of an estrogen-responsive element (ERE) in the proximal promoter of the cyp19b gene. In vivo data in zebrafish have shown that E2 up-regulates AroB only in radial glial cells. This is in agreement with in vitro transfection experiments indicating that this ERE is functional, but not sufficient, as the E2 regulation of AroB only occurs in glial cell contexts, suggesting a cooperation between ER and so far unidentified glial-specific factors. These data also suggest that radial glial cells may express low amounts of ER that escaped detection until now. The expression of AroB in radial cells, well known for their roles in neurogenesis and now considered as progenitor cells, suggests that local E2 production within these cells could influence the well-documented capacity of the brain of teleosts to grow during adulthood.

To obtain a better understanding of the evolution of the brain catecholaminergic systems of fishes, we have examined the distribution of catecholamine-synthesizing enzymes in two species of sturgeon (Acipenser baeri and Huso huso) using antibodies against tyrosine hydroxylase (TH) and dopamine-beta -hydroxylase (DBH; only analyzed in Acipenser). Both sturgeons showed TH-immunoreactive (THir) neurons widely distributed in most regions of the brain, the highest number of THir cells being located in the forebrain (olfactory bulb, preoptic area, and posterior tuberculum). THir cells were also seen in other forebrain areas (retrobulbar area, dorsal and ventral telencephalic areas, hypothalamus, ventral thalamus, pretectal area) and in the brainstem (locus coeruleus, viscerosensory area, caudal reticular formation, and area postrema). Immunoreactive fibers and varicosities showed a wide distribution, being particularly abundant in the diencephalon and mesencephalon. DBH-immunoreactive (DBHir) cells were observed in the anterior tuberal nucleus, where these cells were TH-negative, and in the locus coeruleus and the caudal rhombencephalon (vagal reticular formation), where the DBHir cells were also THir. DBHir fibers were scarce in the telencephalon and very abundant in the diencephalon, mesencephalon, and rhombencephalon. The comparative analysis of the catecholaminergic systems of chondrosteans and those observed in other groups of fishes and tetrapods indicate a similar organization of many nuclei, as well as characteristics that are probably primitive, such as the presence of a large number of forebrain catecholaminergic groups., (Copyright 2002 Wiley-Liss, Inc.)

Using choline acetyltransferase immunocytochemistry, we compared the cholinergic systems of the brains of four groups of fishes (lampreys, elasmobranchs, chondrosteans, and teleosts). Cholinergic nuclei were classified in four groups according to their distribution in vertebrates. The cranial motor nuclei and the habenulo-interpeduncular system were cholinergic in all vertebrates. The cholinergic nuclei of the isthmus of fishes showed many similarities with those of tetrapods. The magnocellular preoptic neurosecretory cells were cholinergic in most fishes, whereas in neurosecretory nuclei of tetrapods, cholinergic cells were only observed adjacent to the magnocellular cells. In the subpallium, cholinergic cells were observed in all fishes, with the exception of elasmobranchs, which suggests that they might be secondarily lost. In the pallium of fishes, cholinergic neurons were only observed in elasmobranchs. Because pallial cholinergic cells were only observed in lizard and mammals, they could have appeared several times during evolution. The same is suggested for the presence of cholinergic cells in the optic tectum of only a few vertebrate groups, including teleosts. This preliminary analysis enlarges our knowledge of the cholinergic systems of fishes, although more species and groups need to be studied to provide a more complete scenario of their evolution.

All studies to date of cholinergic systems of bony fishes have been done in teleosts. To gain further insight into the evolution of the cholinergic systems of bony fishes, we have studied the brain of a chondrostean fish, the Siberian sturgeon (Acipenser baeri, Brandt), by using an antibody against choline acetyltransferase (ChAT). This study showed the presence of ChAT-immunoreactive (ChAT-ir) neurons in the preoptic region (parvocellular and magnocellular preoptic nuclei and suprachiasmatic nucleus), the periventricular and tuberal hypothalamus, the saccus vasculosus, the dorsal thalamus, and the habenula. The mesencephalic tegmentum contained ChAT-ir cells in the torus semicircularis and torus lateralis. The isthmus contained several cholinergic populations: the nucleus isthmi, the lateral nucleus of the valvula, the secondary visceral nucleus, and the dorsal tegmental nucleus. The motor neurons of the cranial nerves and the spinal motor column were strongly immunoreactive. The medial (sensory) trigeminal nucleus also contained a ChAT-ir neuronal population. The distribution of ChAT-ir neurons in the sturgeon brain showed some notable differences with that observed in teleosts, such as the absence of cholinergic cells in the telencephalon and the optic tectum. Several brain regions were richly innervated by ChAT-ir fibers, particularly the telencephalon, optic tectum, thalamus, posterior tubercle, and interpeduncular nucleus. The hypothalamo-hypophyseal tract, the tract of the saccus vasculosus, the fasciculus retroflexus, and an isthmo-mesencephalo-thalamic tract were the most conspicuous cholinergic bundles. Comparative analysis of these results suggests that teleosts have conserved most traits of the cholinergic system of the sturgeon, having acquired new cholinergic populations during evolution., (Copyright 2000 Wiley-Liss, Inc.)

The distribution of serotonin-immunoreactive (5HT-ir) elements was studied in the brain and rostral spinal cord of two chondrosteans, Acipenser baeri and Huso huso, by using an antibody against serotonin. The distribution of these elements was similar in both sturgeon species. In the telencephalon, 5HT-ir cells were found in the olfactory bulb and in the medioventral wall of the telencephalic ventricle, rostral to the anterior commissure, the latter being cerebrospinal fluid-contacting (CSF-C) neurons. The diencephalon contained the highest number of 5HT-ir cell bodies, most of them of CSF-C type, located in the preoptic recess organ, paraventricular organ, posterior recess nucleus, and in the ventromedial thalamus. 5HT-ir non-CSF-C neurons appeared in the dorsal thalamic nucleus. In the brainstem, 5HT-ir neurons were located in four raphe nuclei (dorsal, superior, medial and inferior raphe nuclei) and four lateral reticular nuclei. The dorsal raphe nucleus contained 5HT-ir CSF-C cells, a type of serotoninergic cell that has not been described before in raphe nuclei of fishes or of other vertebrates. CSF-C and non-CSF-C 5HT-ir cells were observed in the spinal cord. 5HT-ir fibers were also widely distributed in the central nervous system of both sturgeon species. Comparison of these results with the distribution of serotoninergic systems in lampreys and other vertebrates suggests that widespread distribution of 5HT-ir cells is a feature of early vertebrate lines.