ABSTRACT
Crinoids belong to the Echinodermata, marine invertebrates with a highly derived adult pentaradial body plan. As the sister group to all other extant echinoderms, crinoids occupy a key phylogenetic position to explore the evolutionary history of the whole phylum. However, their development remains understudied compared with that of other echinoderms. Therefore, the aim here was to establish the Mediterranean feather star (Antedon mediterranea) as an experimental system for developmental biology. We first set up a method for culturing embryos in vitro and defined a standardized staging system for this species. We then optimized protocols to characterize the morphological and molecular development of the main structures of the feather star body plan. Focusing on the nervous system, we showed that the larval apical organ includes serotonergic, GABAergic and glutamatergic neurons, which develop within a conserved anterior molecular signature. We described the composition of the early post-metamorphic nervous system and revealed that it has an anterior signature. These results further our knowledge on crinoid development and provide new techniques to investigate feather star embryogenesis. This will pave the way for the inclusion of crinoids in comparative studies addressing the origin of the echinoderm body plan and the evolutionary diversification of deuterostomes.
Subject(s)
Echinodermata , Embryonic Development , Nervous System , Animals , Echinodermata/genetics , Echinodermata/embryology , Echinodermata/growth & development , Nervous System/embryology , Nervous System/metabolism , Gene Expression Regulation, Developmental , Embryo, Nonmammalian/metabolism , Phylogeny , Biological Evolution , Larva/growth & development , Body PatterningABSTRACT
Despite the lack of endogenous synthesis and relevant nuclear receptors, several papers have been published over the decades claiming that the physiology of mollusks is affected by natural and synthetic sex steroids. With scant evidence for the existence of functional steroid nuclear receptors in mollusks, some scientists have speculated that the effects of steroids might be mediated via membrane receptors (i.e. via non-genomic/non-classical actions) - a mechanism that has been well-characterized in vertebrates. However, no study has yet investigated the ligand-binding ability of such receptor candidates in mollusks. The aim of the present study was to further trace the evolution of the endocrine system by investigating the presence of functional membrane sex steroid receptors in a mollusk, the great pond snail (Lymnaea stagnalis). We detected sequences homologous to the known vertebrate membrane sex steroid receptors in the Lymnaea transcriptome and genome data: G protein-coupled estrogen receptor-1 (GPER1); membrane progestin receptors (mPRs); G protein-coupled receptor family C group 6 member A (GPRC6A); and Zrt- and Irt-like protein 9 (ZIP9). Sequence analyses, including conserved domain analysis, phylogenetics, and transmembrane domain prediction, indicated that the mPR and ZIP9 candidates appeared to be homologs, while the GPER1 and GPRC6A candidates seemed to be non-orthologous receptors. All candidates transiently transfected into HEK293MSR cells were found to be localized at the plasma membrane, confirming that they function as membrane receptors. However, the signaling assays revealed that none of the candidates interacted with the main vertebrate steroid ligands. Our findings strongly suggest that functional membrane sex steroid receptors which would be homologous to the vertebrate ones are not present in Lymnaea. Although further experiments are required on other molluscan model species as well, we propose that both classical and non-classical sex steroid signaling for endocrine responses are specific to chordates, confirming that molluscan and vertebrate endocrine systems are fundamentally different.
Subject(s)
Nervous System , Animals , Nervous System/metabolism , Receptors, Steroid/metabolism , Receptors, Steroid/genetics , Lymnaea/metabolism , Lymnaea/physiology , Mollusca/metabolism , Endocrine System/metabolism , Phylogeny , Receptors, Estrogen/metabolism , Humans , Receptors, Progesterone/metabolism , Gonadal Steroid Hormones/metabolismABSTRACT
The presence of different types of larvae within the same class suggests a broad ecological diversification. A clear comparison of bivalve larval nervous systems would give a broader view on evolutionary and ecological picture of the clade in question. The present study focused on the neurodevelopment in two bivalve species with different larval types: pericalymma of Acila insignis (Bivalvia: Protobranchia) and veliger of Spisula sybillae (Bivalvia: Autobranchia). It was shown that the pioneer dorsal and ventral neurons in S. sybillae appear at the trochophore stage. Subsequently, future three paired ganglia are developed on the nerve cords in pediveliger. In the pericalymma of A. insignis, serotonin- and FMRFamide-positive cells are found in the apical organ (AO), as well as two pairs of FMRFamide positive neurons are detected on dorsal and posterior part of pericalymma. A comparative analysis showed significant differences in the larval neuromorphology between veliger and pericalymma. In contrast to the S. sybillae veliger, the nervous system of the A. insignis pericalymma is simple, likely due to its different lifestyle. The larval nervous system in the species under study has features characteristic of Lophotrochozoa and Spiralia.
Subject(s)
Bivalvia , Larva , Neurogenesis , Animals , Bivalvia/physiology , Neurogenesis/physiology , Larva/physiology , Larva/growth & development , Neurons/physiology , Neurons/cytology , Neurons/metabolism , Nervous SystemSubject(s)
Glucagon-Like Peptide 1 , Neuroprotective Agents , Signal Transduction , Humans , Glucagon-Like Peptide 1/metabolism , Signal Transduction/physiology , Animals , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Nervous System/metabolism , Neuroprotection/physiologyABSTRACT
The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019-2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanisms of action as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories.
Subject(s)
Anti-Inflammatory Agents , Antitubercular Agents , Antiviral Agents , Aquatic Organisms , Biological Products , Hypoglycemic Agents , Humans , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Biological Products/pharmacology , Biological Products/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Nervous System/drug effects , Immune System/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistryABSTRACT
The trematode Acrolichanus auriculatus is a widely distributed intestine parasite of acipenserid fishes. For the first time the localization and distribution of the serotonergic nerve elements in A. auriculatus was studied using immunocytochemical method and confocal laser scanning microscopy. The study revealed the presence of biogenic amine, serotonin, in the central and peripheral nervous systems of A. auriculatus, that is in the neurons and neurites of the brain ganglia, brain commissure, the longitudinal nerve cords, and the connective nerve commissures. The innervation of the attachment organs, pharynx, oesophagus and distal regions of the reproductive system by the serotonergic nerve elements is observed. The distribution of serotonergic neurons in A. auriculatus is schematically marked. The comparative analysis of findings obtained in A. auriculatus with those recorded for other digeneans reveals the presence of both conservative and distinctive features in the organization of the serotonergic nervous system in various representatives of trematodes.
Subject(s)
Fishes , Microscopy, Confocal , Nervous System , Serotonin , Trematoda , Animals , Serotonin/metabolism , Serotonin/analysis , Fishes/parasitology , Serotonergic Neurons/metabolism , ImmunohistochemistryABSTRACT
Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.
Subject(s)
Nervous System , Persistent Organic Pollutants , Prenatal Exposure Delayed Effects , Pregnancy , Humans , Female , Child , Nervous System/drug effects , Nervous System/growth & development , Maternal Exposure/adverse effects , Halogenated Diphenyl Ethers/toxicity , Hydrocarbons, Chlorinated , Child Development/drug effects , Environmental Pollutants/toxicityABSTRACT
Breast cancer (BC) represents a paradigm of heterogeneity, manifesting as a spectrum of molecular subtypes with divergent clinical trajectories. It is fundamentally characterized by the aberrant proliferation of malignant cells within breast tissue, a process modulated by a myriad of factors that govern its progression. Recent endeavors outline the interplay between BC and the nervous system, illuminate the complex symbiosis between neural structures and neoplastic cells, and elucidate nerve dependence as a cornerstone of BC progression. This includes the neural modulations on immune response, neurovascular formation, and multisystem interactions. Such insights have unveiled the critical impact of neural elements on tumor dynamics and patient prognosis. This revelation beckons a deeper exploration into the neuro-oncological interface, potentially unlocking novel therapeutic vistas. This review endeavors to delineate the intricate mechanisms between the nervous system and BC, aiming to accentuate the implications and therapeutic strategies of this intersection for tumor evolution and the formulation of innovative therapeutic approaches.
Subject(s)
Breast Neoplasms , Humans , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Female , Nervous System/metabolism , Nervous System/pathology , Tumor Microenvironment , AnimalsABSTRACT
The sixth SY-Stem Symposium, jointly organized by the Research Institute of Molecular Pathology and the Institute of Molecular Biotechnology took place in Vienna in March 2024. Again, aspiring new group leaders were given a stage to present their work and vision of their labs. To round up the excellent program, the scientific organizers included renowned keynote speakers. Here, we provide a summary of the talks covering topics such as early embryogenesis, nervous system development and disease, regeneration and the latest technologies.
Subject(s)
Embryonic Development , Animals , Humans , Cell Differentiation , Nervous System/embryology , Regeneration/physiology , Stem Cells/cytologyABSTRACT
Taenia crassiceps has been used for decades as an experimental model for the study of human and porcine cysticercosis. Even though, its life cycle, tissue organization, ultrastructure and immune response elicited in the host, have been extensively described, there are many other biological questions remaining to be addressed. In the present study we revisited the muscle and neural architecture of cysticerci in two of the most frequently used strains (WFU and ORF), using conventional staining and confocal microscopy imaging, aiming to assemble an updated anatomy. Differences between both strains, including polarization processes during development of the young budding larvae, are emphasized. We also performed a search for genes that have been related to peptidergic neural processes in other related flatworms. These findings can help to understand the anatomical and molecular consequences of the scolex presence or absence in both strains.
Subject(s)
Cysticercus , Larva , Muscles , Taenia , Animals , Cysticercus/immunology , Muscles/parasitology , Taenia/physiology , Microscopy, Confocal , Cysticercosis/parasitology , Swine , Humans , Nervous SystemABSTRACT
Pain management in neonates continues to be a challenge. Diverse therapies are available that cause loss of pain sensitivity. However, because of side effects, the search for better options remains open. Dexmedetomidine is a promising drug; it has shown high efficacy with a good safety profile in sedation and analgesia in the immature nervous system. Though dexmedetomidine is already in use for pain control in neonates (including premature neonates) and infants as an adjunct to other anesthetics, the question remains whether it affects the neuronal activity patterning that is critical for development of the immature nervous system. In this study, using the neonatal rat as a model, the pharmacodynamic effects of dexmedetomidine on the nervous and cardiorespiratory systems were studied. Our results showed that dexmedetomidine has pronounced analgesic effects in the neonatal rat pups, and also weakly modified both the immature network patterns of cortical and hippocampal activity and the physiology of sleep cycles. Though the respiration and heart rates were slightly reduced after dexmedetomidine administration, it might be considered as the preferential independent short-term therapy for pain management in the immature and developing brain.
Subject(s)
Animals, Newborn , Dexmedetomidine , Dexmedetomidine/pharmacology , Animals , Rats , Analgesics, Non-Narcotic/pharmacology , Analgesia/methods , Pain Management/methods , Male , Rats, Sprague-Dawley , Pain/drug therapy , Heart Rate/drug effects , Female , Nervous System/drug effects , Nervous System/growth & developmentABSTRACT
Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this 'superficial' simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction.
Subject(s)
Nervous System , Neurogenesis , Animals , Nervous System/growth & development , Nervous System/embryology , Neurogenesis/physiology , Platyhelminths/growth & development , Platyhelminths/physiology , Biological Evolution , Neurons/cytology , Neurons/physiologyABSTRACT
In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children's health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer's, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.
Subject(s)
Maternal Exposure , Toluene , Humans , Toluene/toxicity , Female , Infant , Maternal Exposure/adverse effects , Pregnancy , Adult , Nervous System/drug effects , Nervous System/embryology , Nervous System/metabolism , Nervous System/growth & development , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Epigenesis, Genetic/drug effects , Male , Mothers , Air Pollutants/toxicity , Infant, NewbornABSTRACT
Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated with stress and cellular damage. TLRs are expressed in resident immune cells and both neurons and glial cells of the nervous system. Increasing evidence is emerging on the participation of TLRs not only in the immune response but also in processes of the nervous system, such as neurogenesis and cognition. Below, we present a review of the literature that evaluates the expression and role of TLRs in processes such as neurodevelopment, behavior, cognition, infection, neuroinflammation, and neurodegeneration.
Subject(s)
Nervous System , Neurogenesis , Toll-Like Receptors , Humans , Toll-Like Receptors/metabolism , Animals , Nervous System/metabolism , Nervous System/immunology , Immunity, Innate , Neurons/metabolism , Neurons/immunology , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/immunology , Signal TransductionABSTRACT
The California sea hare (Aplysia californica) is a model for age associated cognitive decline. Recent researched identified a novel nidovirus, Aplysia Abyssovirus 1, with broad tropism enriched in the Aplysia nervous system. This virus is ubiquitous in wild and maricultured, young and old animals without obvious pathology. Here we re-evaluated gene expression data from several previous studies to investigate differential expression in the nervous system and gill in response to virus and aging as well as the mutational spectrum observed in the viral sequences obtained from these datasets. Viral load and age were highly correlated, indicating persistent infection. Upregulated genes in response to virus were enriched for immune genes and signatures of ER and proteostatic stress, while downregulated genes were enriched for mitochondrial metabolism. Differential expression with respect to age suggested increased iron accumulation and decreased glycolysis, fatty acid metabolism, and proteasome function. Interaction of gene expression trends associated with viral infection and aging suggest that viral infection likely plays a role in aging in the Aplysia nervous system. Mutation analysis of viral RNA identified signatures suggesting ADAR and AID/APOBEC like deaminase act as part of Aplysia anti-viral defense.
Subject(s)
Aplysia , Nodaviridae , Animals , Aging/immunology , Aplysia/immunology , Gills/virology , Gills/immunology , Host-Pathogen Interactions/immunology , Nervous System/virology , Nervous System/immunology , Nodaviridae/physiology , RNA, Viral/genetics , Viral LoadABSTRACT
Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-ß-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.
Subject(s)
Copper , Humans , Copper/metabolism , Animals , Homeostasis/physiology , Nervous System/metabolismABSTRACT
While classical NOD-like receptor pyrin domain containing protein 1 (NLRP1) and NLRP3 inflammasomal proteins have been extensively investigated, the contribution of NLRP2 is still ill-defined in the nervous system. Given the putative significance of NLRP2 in orchestrating neuroinflammation, further inquiry is needed to gain a better understanding of its connectome, hence its specific targeting may hold a promising therapeutic implication. Therefore, bioinformatical approach for extracting information, specifically in the context of neuropathologies, is also undoubtedly preferred. To the best of our knowledge, there is no review study selectively targeting only NLRP2. Increasing, but still fragmentary evidence should encourage researchers to thoroughly investigate this inflammasome in various animal- and human models. Taken together, herein we aimed to review the current literature focusing on the role of NLRP2 inflammasome in the nervous system and more importantly, we provide an algorithm-based protein network of human NLRP2 for elucidating potentially valuable molecular partnerships that can be the beginning of a new discourse and future therapeutic considerations.
Subject(s)
Apoptosis Regulatory Proteins , Inflammasomes , Humans , Inflammasomes/metabolism , Animals , Apoptosis Regulatory Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Nervous System/metabolismABSTRACT
Recent advancements in understanding the tumor microenvironment (TME) have highlighted the critical role of the nervous system in cancer progression. This review comprehensively examines how the nervous system influences various aspects of tumorigenesis, including growth, motility, immune response, angiogenesis, and the behavior of cancer-associated fibroblasts (CAFs). We delineate the neurodevelopmental mechanisms associated with cancer, such as the secretion of neurotrophins and exosomes by cancer cells. Furthermore, we explore the emerging therapeutic strategy of targeting nerves associated with tumors. Evidence supporting this approach includes studies demonstrating direct tumor growth inhibition, enhanced efficacy of immunotherapy when combined with nervous system-modulating drugs, and the suppression of tumor blood vessel formation through nerve targeting. Finally, we discuss the current challenges in this field and emphasize the need for further exploration within cancer neuroscience.
Subject(s)
Neoplasms , Tumor Microenvironment , Humans , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/metabolism , Animals , Nervous System/metabolism , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Neovascularization, Pathologic , Immunotherapy/methodsABSTRACT
Drosophila nervous system development progresses through a series of well-characterized steps in which homeodomain transcription factors (HDTFs) play key roles during most, if not all, phases. Strikingly, although some HDTFs have only one role, many others are involved in multiple steps of the developmental process. Most Drosophila HDTFs engaged in nervous system development are conserved in vertebrates and often play similar roles during vertebrate development. In this Spotlight, we focus on the role of HDTFs during embryogenesis, where they were first characterized.