Pattern of Nitrergic Neuronal System Organization in the Brain of Two Holostean Fishes (Actinopterygii: Ginglymodi)

The study of the nitrergic system, formed by the networks of neurons containing the enzyme nitric oxide synthase (NOS), has been extremely useful in unraveling neuroanatomical features of the organization of the central nervous system of vertebrates. Thus, data are available for representatives of most vertebrate classes and, in particular, several studies have detailed the organization of this system in teleosts. In contrast, no information is available regarding this neurotransmission system in the brains of holosteans, an early diverged and poorly understood group of actinopterygian fishes, currently considered a sister group of teleosts that contains only 8 species. The present study provides the first detailed information on the distribution of nitrergic cell bodies and fibers in 2 holostean species of the genus Lepisosteus, the spotted gar L. oculatus and the Florida gar L. platyrhincus. NOS immunohistochemistry and the NADPH diaphorase (NADPH-d) histochemical reaction were used, and both techniques yielded identical results, with the exception of the primary olfactory and terminal nerve fibers, which only labeled for NADPH-d exclusively in L. oculatus. Double immunohistochemistry was conducted for the simultaneous detection of NOS with tyrosine hydroxylase, choline acetyltransferase, calbindin, calretinin, and serotonin to accurately establish the localization of the nitrergic neurons and fibers in the brain of holosteans, the neuroanatomy of which has been mostly neglected, and to assess possible interactions between these neuroactive substances. Distinct groups of nitrergic cells were located in subpallial areas, the basal hypothalamus, posterior tubercle, optic tectum and mesencephalic tegmentum, reticular formation, solitary tract nucleus, spinal cord, and amacrine cells in the retina. In addition, low numbers of nitrergic cells were observed in the pallium, suprachiasmatic nucleus, prethalamic and thalamic areas, torus lateralis and torus semicircularis, cerebellar and laterodorsal tegmental nuclei, and the ventral octavolateral area. Comparison of these results with those from other classes of vertebrates, and including a segmental analysis to correlate cell populations, reveals that the pattern of the nitrergic system in holosteans is very close to that in ancestral actinopterygian fishes and highlights conserved and derived traits.

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Organization of the Orexin/Hypocretin System in the Brain of Holostean Fishes: Assessment of Possible Relationships with Monoamines and Neuropeptide Y

Brain Behavior and Evolution ◽

10.1159/000490172 ◽

2018 ◽

Vol 91 (4) ◽

pp. 228-251 ◽

Cited By ~ 2

Author(s):

Daniel Lozano ◽

Agustín González ◽

Jesús M. López

Keyword(s):

Neuropeptide Y ◽

Simultaneous Detection ◽

Sister Group ◽

Spotted Gar ◽

Cell Groups ◽

Actinopterygian Fishes ◽

The Central Nervous System ◽

Amia Calva ◽

Lepisosteus Oculatus ◽

The Brain

Holosteans form a small group of actinopterygian fishes considered the sister group of teleosts. Despite this proximity to the biggest group of vertebrates, relatively few studies have been conducted to investigate the organization of the central nervous system of this group of fishes. In this study, the neuroanatomical distribution of orexin/hypocretin-like immunoreactive (OX-ir) cell bodies and fibers was analyzed in the brain of 3 representative species of the 2 orders of extant holosteans, the spotted gar Lepisosteus oculatus, the Florida gar Lepisosteus platyrhincus, and the bowfin Amia calva. Antibodies against orexin-A (OXA) and orexin-B (OXB) were used, which labeled the same cells and fibers throughout the brain. In addition, double immunohistofluorescence was performed for the simultaneous detection of OXA and OXB with tyrosine hydroxylase, serotonin, and neuropeptide Y (NPY), in an attempt to localize the orexinergic structures precisely and study the possible interactions between these neuroactive substances. The pattern of distribution of OX-ir cells in the 3 species was largely similar, showing labeled cells in the preoptic area (POA), and the tuberal and retrotuberal hypothalamic regions, with only subtle differences between species in the density of labeled cells. OX-ir fibers were found in all main brain subdivisions of the 3 species, mostly in the ventral subpallial areas, POA, hypothalamus, posterior tubercle, thalamus, and mesencephalic tectum. Different densities of orexinergic fibers were observed in relation to catecholaminergic and serotoninergic cell groups, as well as an absence of colocalization between orexins and NPY in the same hypothalamic neurons. The comparison of these results with those obtained in other vertebrates highlights a constant pattern of distribution of this system of neurotransmission among different groups of actinopterygian fishes, especially in teleosts. Conserved features shared by all vertebrates studied were also observed, such as the presence of OX-ir cells in the basal hypothalamus, reflecting the preserved functions of these neuropeptides over the course of evolution.

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Neuroanatomical Distribution of the Serotonergic System in the Brain and Retina of Holostean Fishes, The Sister Group to Teleosts

Brain Behavior and Evolution ◽

10.1159/000505473 ◽

2020 ◽

Vol 95 (1) ◽

pp. 25-44

Author(s):

Daniel Lozano ◽

Agustín González ◽

Jesús M. López

Keyword(s):

Spinal Cord ◽

Preoptic Area ◽

Area Postrema ◽

Sister Group ◽

Brain Regions ◽

Serotonergic System ◽

Paraventricular Organ ◽

Cell Groups ◽

Actinopterygian Fishes ◽

The Brain

Among actinopterygian fishes, holosteans are the phylogenetically closest group to teleosts but they have been much less studied, particularly regarding the neurochemical features of their central nervous system. The serotonergic system is one of the most important and conserved systems of neurotransmission in all vertebrates. By means of immunohistochemistry against serotonin (5-hydroxytryptamine), we have conducted a comprehensive and complete description of this system in the brain and retina of representative species of the 3 genera of holostean fishes, belonging to the only 2 extant orders, Amiiformes and Lepisosteiformes. Serotonin-immunoreactive cell groups were detected in the preoptic area, the hypothalamic paraventricular organ, the epiphysis, the pretectal region, the long and continuous column of the raphe, the spinal cord, and the inner nuclear layer of the retina. Specifically, the serotonergic cell groups in the preoptic area, the epiphysis, the pretectum, and the retina had never been identified in previous studies in this group of fishes. Widespread serotonergic innervation was observed in all main brain regions, but more abundantly in the subpallium, the hypothalamus, the habenula, the optic tectum, the so-called cerebellar nucleus, and the area postrema. The comparative analysis of these results with those in other groups of vertebrates reveals some extremely conserved features, such as the presence of serotonergic cells in the retina, the pineal organ, and the raphe column, while other characteristics, like the serotonergic populations in the preoptic area, the paraventricular organ, the pretectum, and the spinal cord are generally present in all fish groups, but have been lost in most amniotes.

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Comparative Analysis of the Organization of the Catecholaminergic Systems in the Brain of Holostean Fishes (Actinopterygii/Neopterygii)

Brain Behavior and Evolution ◽

10.1159/000503769 ◽

2019 ◽

Vol 93 (4) ◽

pp. 206-235

Author(s):

Daniel Lozano ◽

Ruth Morona ◽

Agustín González ◽

Jesús M. López

Keyword(s):

Preoptic Area ◽

Area Postrema ◽

Sister Group ◽

Representative Species ◽

Cell Groups ◽

Actinopterygian Fishes ◽

Amia Calva ◽

Lepisosteus Oculatus ◽

Atractosteus Spatula ◽

The Brain

Living holosteans, comprising 8 species of bowfins and gars, form a small monophyletic group of actinopterygian fishes, which are currently considered as the sister group to the enormously numerous teleosts and have largely been neglected in neuroanatomical studies. We have studied the catecholaminergic (CAergic) systems by means of antibodies against tyrosine hydroxylase (TH) and dopamine (DA) in the brain of representative species of the 3 genera included in the 2 orders of holostean fishes: Amia calva (Amiiformes) and Lepisosteus platyrhincus, Lepisosteus oculatus, and Atractosteus spatula (Lepisosteiformes). Different groups of TH/DA-immunoreactive (ir) cells were observed in the olfactory bulb, subpallium, and preoptic area of the telencephalon. Hypothalamic groups were labeled in the suprachiasmatic nucleus, tuberal (only in A. calva), retrotuberal, and retromamillary areas; specifically, the paraventricular organ showed only DA immunoreactivity. In the diencephalon, TH/DA-ir groups were detected in the prethalamus, posterior tubercle, and pretectum. In the caudal hindbrain, the solitary tract nucleus and area postrema presented TH/DA-ir cell groups, and also the spinal cord and the retina. Only in A. calva, particular CAergic cell groups were observed in the habenula, the mesencephalic tegmentum, and in the locus coeruleus. Following a neuromeric analysis, the comparison of these results with those obtained in other classes of fishes and tetrapods shows many common traits of CAergic systems shared by most vertebrates and in addition highlights unique features of actinopterygian fishes.

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HISTOLOGY AND HISTOCHEMISTRY OF THE PINEAL ORGAN IN THE SOCKEYE SALMON, ONCORHYNCHUS NERKA WALBAUM

Canadian Journal of Zoology ◽

10.1139/z67-014 ◽

1967 ◽

Vol 45 (1) ◽

pp. 117-126 ◽

Cited By ~ 20

Author(s):

M. A. Hafeez ◽

P. Ford

Keyword(s):

Sockeye Salmon ◽

Pineal Organ ◽

Subcommissural Organ ◽

Sensory Nerve ◽

Nerve Fibers ◽

Supporting Cells ◽

Dependent Behavior ◽

Aldehyde Fuchsin ◽

Pineal Nerve ◽

The Brain

The morphohistology and some histochemical aspects of the pineal organ in the sockeye salmon were studied. The distal part of the organ lies in a pineal fossa in the cranial roof. Photosensory cells and two kinds of ependymal supporting cells are present throughout its epithelium, which is entirely devoid of either melanin or lipofuchsin. Besides sensory nerve fibers, efferent end-loops are present on the photosensory as well as the supporting cells. The dorsal pineal nerve tract probably contains both sensory and efferent fibers. The apocrine secretion of sensory as well as some supporting cells is probably associated with either the maintenance of a constant chemical composition of the cerebrospinal fluid or with supply of certain chemical substances to the brain tissue. The secretion in the pineal and the subcommissural organ consists of glycogen, mucopolysaccharides, mucoproteins, and aldehyde fuchsin positive granules.It is proposed that the pineal organ is photosensory as well as secretory and that its photosensitivity might be of some significance in the light-dependent behavior of this species in terms of intensity detection.

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VIRTUAL SCREENING OF BETA-SECRETASE 1 (BACE1) INHIBITORS IN THE INDONESIAN HERBAL DATABASE AS USING AUTODOCK AND AUTODOCK VINA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10s5.23119 ◽

2017 ◽

Vol 10 (17) ◽

pp. 148

Author(s):

Asti Anna Tanisa ◽

Rezi Riadhi

Keyword(s):

Binding Energy ◽

Virtual Screening ◽

Cellular Response ◽

Senile Plaque ◽

Area Under The Curve ◽

Neuronal System ◽

Operating Characteristics ◽

Autodock Vina ◽

Beta Secretase ◽

The Brain

Objective: Alzheimer’s is a neurodegenerative disease caused by the accumulation of senile plaque in the brain that affects neuronal system leading to a less sensitive cellular response from neurons. Previous research has found that beta-secretase 1 (BACE1) plays an important role in the senile plaque formation, become a target in Alzheimer’s medication.Methods: In this study, virtual screening of BACE1 inhibitors on the Indonesian Herbal Database was done using AutoDock and AutoDock Vina. The screening was validated using the directory of useful decoys: Enhanced database. Parameters for validation process of AutoDock and AutoDock Vina are enrichment factor (EF), receiver operating characteristics, and area under the curve (AUC).Results: The dimensions of grid boxes were 30×30×30 (AutoDock) and 11.25×11.25×11.25 (AutoDock Vina). The EF 1% and AUC values obtained from the AutoDock are 7.74 and 0.73, respectively, and in the AutoDock Vina are 4.6 and 0.77, respectively. Based on the virtual screening results, the top six compounds obtained using AutoDock (binding energy ranging from −7.84 kcal/mol to −8.79 kcal/mol) include: Azadiradione, cylindrin, lanosterol, sapogenin, simiarenol, and taraxerol. The top seven compounds (binding energy ranging from −8.8 kcal/mol to −9.4 kcal/mol) obtained using AutoDeck Vina include: Bryophyllin A, diosgenin, azadiradione, sojagol, beta-amyrin, epifriedelinol, and jasmolactone C.Conclusions: Only azadiradione was obtained from the virtual screening conducted using both types of software; it interacts with the active region in BACE1 at residue Trp 76 (AutoDock result) and Thr 232 (AutoDock Vina result).

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Nondestructive imaging of the internal microstructure of vessels and nerve fibers in rat spinal cord using phase-contrast synchrotron radiation microtomography

Journal of Synchrotron Radiation ◽

10.1107/s1600577517000121 ◽

2017 ◽

Vol 24 (2) ◽

pp. 482-489 ◽

Cited By ~ 9

Author(s):

Jianzhong Hu ◽

Ping Li ◽

Xianzhen Yin ◽

Tianding Wu ◽

Yong Cao ◽

...

Keyword(s):

Spinal Cord ◽

Synchrotron Radiation ◽

Phase Contrast ◽

Three Dimensional ◽

Nerve Fibers ◽

The Body ◽

Rat Spinal Cord ◽

Nondestructive Imaging ◽

Synchrotron Radiation Microtomography ◽

The Brain

The spinal cord is the primary neurological link between the brain and other parts of the body, but unlike those of the brain, advances in spinal cord imaging have been challenged by the more complicated and inhomogeneous anatomy of the spine. Fortunately with the advancement of high technology, phase-contrast synchrotron radiation microtomography has become widespread in scientific research because of its ability to generate high-quality and high-resolution images. In this study, this method has been employed for nondestructive imaging of the internal microstructure of rat spinal cord. Furthermore, digital virtual slices based on phase-contrast synchrotron radiation were compared with conventional histological sections. The three-dimensional internal microstructure of the intramedullary arteries and nerve fibers was vividly detected within the same spinal cord specimen without the application of a stain or contrast agent or sectioning. With the aid of image post-processing, an optimization of vessel and nerve fiber images was obtained. The findings indicated that phase-contrast synchrotron radiation microtomography is unique in the field of three-dimensional imaging and sets novel standards for pathophysiological investigations in various neurovascular diseases.

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Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain

Frontiers in Neuroanatomy ◽

10.3389/fnana.2021.767223 ◽

2021 ◽

Vol 15 ◽

Author(s):

Miriam Menzel ◽

Marouan Ritzkowski ◽

Jan A. Reuter ◽

David Gräßel ◽

Katrin Amunts ◽

...

Keyword(s):

Human Brain ◽

Nerve Fiber ◽

Brain Tissue ◽

Scattered Light ◽

Polar Angle ◽

Nerve Fibers ◽

Fiber Architecture ◽

Whole Brain ◽

Tissue Samples ◽

The Brain

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

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Primary Peripheral Epstein-Barr Virus Infection Can Lead to CNS Infection and Neuroinflammation in a Rabbit Model: Implications for Multiple Sclerosis Pathogenesis

10.21203/rs.3.rs-792416/v1 ◽

2021 ◽

Author(s):

Asma Hassani ◽

Narendran Reguraman ◽

Safa Shehab ◽

Gulfaraz Khan

Keyword(s):

Multiple Sclerosis ◽

Epstein Barr Virus ◽

Rabbit Model ◽

Nerve Fibers ◽

Cns Infection ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

Cellular Aggregates ◽

The Brain

Abstract Background: Epstein-Barr virus (EBV) is a common herpesvirus associated with malignant and non-malignant conditions. An accumulating body of evidence supports a role for EBV in the pathogenesis of multiple sclerosis (MS), a demyelinative disease of the CNS. However, little is known about the details of the link between EBV and MS. One obstacle which has hindered research in this area has been the lack of a suitable animal model recapitulating natural infection in humans. We have recently shown that healthy rabbits are susceptible to EBV infection, and viral persistence in these animals mimics latent infection in humans. Methods: We used the rabbit model to investigate if peripheral EBV infection can lead to infection of the CNS and its potential consequences. We injected EBV intravenously in one group of animals, and PBS in another, with and without immunosuppression. Histopathological changes and viral dynamics were examined in peripheral blood, spleen, brain, and spinal cord, using a range of molecular and histopathology techniques. Results: Our investigations uncovered important findings that could not be previously addressed. We showed that primary peripheral EBV infection can lead to the virus traversing the CNS. Cell associated, but not free virus in the plasma, correlated with CNS infection. The infected cells within the brain were found to be B-lymphocytes. Most notably, animals injected with EBV, but not PBS, developed inflammatory cellular aggregates in the CNS. The incidence of these aggregates increased in the immunosuppressed animals. The cellular aggregates contained compact clusters of macrophages surrounded by reactive astrocytes and dispersed B and T lymphocytes, but not myelinated nerve fibers. Moreover, studying EBV infection over a span of 28 days, revealed that the peak point for viral load in the periphery and CNS coincides with increased occurrence of cellular aggregates in the brain. Finally, peripheral EBV infection triggered temporal changes in the expression of latent viral transcripts and cytokines in the brain. Conclusion: The present study provides the first direct in vivo evidence for the role of peripheral EBV infection in CNS pathology, and highlights a unique model to dissect viral mechanisms contributing to the development of MS.

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Activity-dependent, homeostatic regulation of neurotransmitter release from auditory nerve fibers

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1420885112 ◽

2015 ◽

Vol 112 (20) ◽

pp. 6479-6484 ◽

Cited By ~ 21

Author(s):

Tenzin Ngodup ◽

Jack A. Goetz ◽

Brian C. McGuire ◽

Wei Sun ◽

Amanda M. Lauer ◽

...

Keyword(s):

Auditory Nerve ◽

Neurotransmitter Release ◽

High Reliability ◽

Downstream Processing ◽

Nerve Fibers ◽

Synaptic Activity ◽

Quantal Size ◽

Activity Dependent ◽

The Brain ◽

Homeostatic Response

Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low Pr. For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased Pr. These changes in N and Pr were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activity-dependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences.

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Quality of Life Philosophy IV. The Brain and Consciousness

The Scientific World JOURNAL ◽

10.1100/tsw.2003.104 ◽

2003 ◽

Vol 3 ◽

pp. 1199-1209 ◽

Cited By ~ 4

Author(s):

Søren Ventegodt ◽

Niels Jørgen Andersen ◽

Joav Merrick

Keyword(s):

Quality Of Life ◽

Medical Science ◽

Nerve Fibers ◽

Real Problem ◽

Philosophical Perspective ◽

Garden Of Eden ◽

The World ◽

Life Philosophy ◽

The Brain

In this article we look at the brain’s structure and function from a philosophical perspective. Although the brain at micro-level, with its trillions of ultra-thin nerve fibers, is one of the most complicated structures in the known universe, you can still grasp its composition if you go up to the level of the cell. How this structure functions is not quite clear. You can understand its function at fiber level, because it is fairly simple, and you can understand it at cell level, but it is already vague. Roughly speaking, you can envision a single nerve cell as a tiny, independent computer whose behavior is dependent on continuous calculations of all input. At organ level, the function can be understood as an extremely complex pattern machine. Finally, the brain’s function can be understood at the cognitive level as what provides consciousness through its ability to keep order in our complicated reality. The superior function of the brain is to connect the real us, our higher self, to the surrounding world.The brain has been developed so that it can create all possible complex patterns. The connectivity seems to imply that the patterns of the human brain are 1000-dimensional. It is our vision that these complicated patterns arise from basic patterns in the quantum matter of which everything is created. In our opinion, our consciousness’ special utilization of a patterned aspect of nature is what lies behind inscrutable statements like “Man is created in God’s image”. We suggest that these patterns in matter are the basic, creative force that influences all living organisms. Unfortunately, science has only just begun to understand these patterns.The Bible’s description of the origin of man is two people eating from the Tree of Knowledge and as punishment they are expelled from the Garden of Eden. What does that mean? It means that, as conscious creatures, we no longer were an unproblematic, harmonious part of the world around us. The great question is why this consciousness about the world, provided by the brain, is not a gift that makes life better instead of getting us expelled from the Garden of Eden. We think that our real problem is the fact that we are still not in control of our consciousness. Instead of it serving us, we have become its slaves. If we come to understand brain and consciousness in order to solve this basic problem of our existence, we shall again be able to become a coherent part of the world, both as individuals and as a species. We share the vision that such an understanding of the problems of consciousness will make medical science holistic and will bring quality of life, health, and the ability to function to its patients.

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