Our understanding of the multiorgan pathology of cystic fibrosis (CF) has improved impressively during the last decades, but we still lack a full comprehension of the disease progression. Animal ...models have greatly contributed to the elucidation of specific mechanisms involved in CF pathophysiology and the development of new therapies. Soon after the cloning of the CF transmembrane conductance regulator (
) gene in 1989, the first mouse model was generated and this model has dominated
CF research ever since. Nonetheless, the failure of murine models to mirror human disease severity in the pancreas and lung has led to the generation of larger animal models such as pigs and ferrets. The following review presents and discusses data from the current animal models used in CF research.
A wide variety of human diseases have been modelled in zebrafish, including various types of cancer, cardiovascular diseases and neurodegenerative diseases like Alzheimer's and Parkinson's. Recent ...reviews have summarized the currently available zebrafish models of Parkinson's Disease, which include gene-based, chemically induced and chemogenetic ablation models. The present review updates the literature, critically evaluates each of the available models of Parkinson's Disease in zebrafish and compares them with similar models in invertebrates and mammals to determine their advantages and disadvantages. We examine gene-based models, including ones linked to Early-Onset Parkinson's Disease:
, and
; but we also examine
which is linked to Late-Onset Parkinson's Disease. We evaluate chemically induced models like MPTP, 6-OHDA, rotenone and paraquat, as well as chemogenetic ablation models like metronidazole-nitroreductase. The article also reviews the unique advantages of zebrafish, including the abundance of behavioural assays available to researchers and the efficiency of high-throughput screens. This offers a rare opportunity for assessing the potential therapeutic efficacy of pharmacological interventions. Zebrafish also are very amenable to genetic manipulation using a wide variety of techniques, which can be combined with an array of advanced microscopic imaging methods to enable
visualization of cells and tissue. Taken together, these factors place zebrafish on the forefront of research as a versatile model for investigating disease states. The end goal of this review is to determine the benefits of using zebrafish in comparison to utilising other animals and to consider the limitations of zebrafish for investigating human disease.
Each zebrafish olfactory bulb contains ~ 140 glomeruli that are distinguishable based on size, location, neurochemistry and function. Here we examine the mitral cell innervation of differently sized ...glomeruli in adult zebrafish. Type 1 glomeruli had diameters of 80.9 ± 8.1 μm and were innervated by 5.9 ± 0.9 mitral cells. The Type 1 mediodorsal glomeruli (mdG) were innervated by both uniglomerular (innervating only single glomeruli) and multiglomerular mitral cells (innervating two or more glomeruli). In contrast, the Type 1 ventroposterior (vpG) and lateral glomeruli (lG) were only innervated by uniglomerular mitral cells. Type 2 ventral glomeruli were 46 ± 5.1 μm in diameter and were innervated by 3.3 ± 0.2 mitral cells. Type 2 ventromedial glomeruli (vmG) were innervated exclusively by uniglomerular mitral cells. Type 3 glomeruli had diameters of 17 ± 2.5 μm and were innervated by 1.1 ± 0.6 multiglomerular mitral cells each. Finally, Type 4 glomeruli were small, with average diameters of 4.8 ± 3.9 μm and were restricted to the lateral plexus. These glomeruli were innervated mainly by multiglomerular mitral cells with extensively branching dendrites. This study provides the first specific associations between uni- and multiglomerular mitral cells with known zebrafish glomeruli. Our results suggest that glomeruli are distinguishable based on their postsynaptic compartment and that distinct input–output computations occur in different types of zebrafish glomeruli.
The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the ...relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons.
Sex steroids, as well as their major metabolic enzymes and pathways, have been widely identified in molluscs, although evidence for their involvement in the control of reproduction is less ...established. Recent attention on endocrine disrupting chemical pollutants and potential for improvements in aquaculture provide strong incentives for better understanding potential functions of these substances in normal molluscan physiology. The aim of this review is to present the state of knowledge of possible roles of sex steroids in bivalves, with emphasis on recent progress in the field. In particular, recent studies on scallops, which are used widely in aquaculture, have demonstrated that injections of estradiol, testosterone, progesterone and dehydroepiandrosterone (DHEA) significantly promoted sexual differentiation and shifted sex ratios, resulting in more males than females, as well as causing other morphological changes. In vitro experiments demonstrated that estradiol and progesterone potentiated serotonin-induced gamete release in both sexes while testosterone was only effective in males. Examinations of the time scales of these effects and pharmacological studies utilizing antisteroids or RNA or protein synthesis inhibitors suggested that these effects may be mainly mediated by intracellular sex steroid receptors. Similar effects were also obtained by in vivo injections of these steroids. Radioligand binding studies suggest that specific estrogen binding sites exist in the cytosolic and nuclear fractions of both female and male scallop gonads, and translocation of these estrogen binding sites may be involved in the sexual maturation of scallops. Using degenerate primers based upon nucleotide sequences of vertebrate estrogen receptors, further attempts have been made to characterize the sequence and expression patterns of a possible scallop estrogen receptor gene. Such studies thus suggest that sex steroids may play an important role in the reproductive control of the scallops, possibly through the activation of sex steroid receptors.
Cephalopods are radically different from any other invertebrate. Their molluscan heritage, innovative nervous system, and specialized behaviors create a unique blend of characteristics that are ...sometimes reminiscent of vertebrate features. For example, despite differences in the organization and development of their nervous systems, both vertebrates and cephalopods use many of the same neurotransmitters. One neurotransmitter, histamine (HA), has been well studied in both vertebrates and invertebrates, including molluscs. While HA was previously suggested to be present in the cephalopod central nervous system (CNS), Scaros, Croll, and Baratte only recently described the localization of HA in the olfactory system of the cuttlefish Sepia officinalis. Here, we describe the location of HA using an anti‐HA antibody and a probe for histidine decarboxylase (HDC), a synthetic enzyme for HA. We extended previous descriptions of HA in the olfactory organ, nerve, and lobe, and describe HDC staining in the same regions. We found HDC‐positive cell populations throughout the CNS, including the optic gland and the peduncle, optic, dorso‐lateral, basal, subvertical, frontal, magnocellular, and buccal lobes. The distribution of HA in the olfactory system of S. officinalis is similar to the presence of HA in the chemosensory organs of gastropods but is different than the sensory systems in vertebrates or arthropods. However, HA's widespread abundance throughout the rest of the CNS of Sepia is a similarity shared with gastropods, vertebrates, and arthropods. Its widespread use with differing functions across Animalia provokes questions regarding the evolutionary history and adaptability of HA as a transmitter.
We describe the location of histamine (HA) using an anti‐HA antibody and a probe for histidine decarboxylase (HDC) in the common cuttlefish, Sepia officinalis. We expand upon previous descriptions of HA in the olfactory organ, nerve, and lobe. HDC‐positive cell populations were found throughout the central nervous system. The distribution of HA in the olfactory system of S. officinalis has implications for the evolution of olfaction across the animal kingdom and the versatility of HA as a neurotransmitter.
Terrestrial animals must support their bodies against gravity, while aquatic animals are effectively weightless because of buoyant support from water. Given this evolutionary history of minimal ...gravitational loading of fishes in water, it has been hypothesized that weight-responsive musculoskeletal systems evolved during the tetrapod invasion of land and are thus absent in fishes. Amphibious fishes, however, experience increased effective weight when out of water - are these fishes responsive to gravitational loading? Contrary to the tetrapod-origin hypothesis, we found that terrestrial acclimation reversibly increased gill arch stiffness (∼60% increase) in the amphibious fish
when loaded normally by gravity, but not under simulated microgravity. Quantitative proteomics analysis revealed that this change in mechanical properties occurred via increased abundance of proteins responsible for bone mineralization in other fishes as well as in tetrapods. Type X collagen, associated with endochondral bone growth, increased in abundance almost ninefold after terrestrial acclimation. Collagen isoforms known to promote extracellular matrix cross-linking and cause tissue stiffening, such as types IX and XII collagen, also increased in abundance. Finally, more densely packed collagen fibrils in both gill arches and filaments were observed microscopically in terrestrially acclimated fish. Our results demonstrate that the mechanical properties of the fish musculoskeletal system can be fine-tuned in response to changes in effective body weight using biochemical pathways similar to those in mammals, suggesting that weight sensing is an ancestral vertebrate trait rather than a tetrapod innovation.
Developmental programmes for many marine invertebrates include the assembly of muscular systems appropriate to the functions of swimming and feeding in pelagic larvae. Upon metamorphosis, that ...musculature is often radically re‐organized to meet very different demands of post‐larval life. To investigate the development and fate of musculature in the nudibranch Phestilla sibogae, embryos, larvae and metamorphosing stages were fixed, labelled with phalloidin and examined with confocal microscopy. The resultant images revealed the sequential development of both large retractor muscles and numerous finer muscles that allow the larva to manipulate the velum, foot and operculum. Observations of living specimens at the same stages as those fixed for microscopy revealed the actions of the muscles as they developed. During metamorphosis, muscles with shell attachments disintegrate as the larva transforms into a shell‐less juvenile. Notably, the massive velar, pedal and opercular retractor muscles disappear during metamorphosis in a sequence that corresponds to their loss of function. Other muscles, however, that appear to be important to the embryo and free‐swimming larva persist into juvenile life. The comprehensive and detailed observations of the musculature presented here provide a solid foundation for comparisons with other species with different phylogenies and life histories.
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