Flatworm nerve–muscle: structural and functional analysis

2004 ◽  
Vol 82 (2) ◽  
pp. 316-333 ◽  
Author(s):  
D W Halton ◽  
A G Maule
Keyword(s):  
Nervous System ◽  
Second Messengers ◽  
Signal Transduction Pathway ◽  
Neuronal Cell ◽  
Cell Types ◽  
Confocal Imaging ◽  
Muscle Fibres ◽  
Messenger Molecules ◽  
Baseline Information ◽  
Nerve Muscle

Platyhelminthes occupy a unique position in nerve–muscle evolution, being the most primitive of metazoan phyla. Essentially, their nervous system consists of an archaic brain and associated pairs of longitudinal nerve cords cross-linked as an orthogon by transverse commissures. Confocal imaging reveals that these central nervous system elements are in continuity with an array of peripheral nerve plexuses which innervate a well-differentiated grid work of somatic muscle as well as a complexity of myofibres associated with organs of attachment, feeding, and reproduction. Electrophysiological studies of flatworm muscles have exposed a diversity of voltage-activated ion channels that influence muscle contractile events. Neuronal cell types are mainly multi- and bi-polar and highly secretory in nature, producing a heterogeneity of vesicular inclusions whose contents have been identified cytochemically to include all three major types of cholinergic, aminergic, and peptidergic messenger molecules. A landmark discovery in flatworm neuro biology was the biochemical isolation and amino acid sequencing of two groups of native neuropeptides: neuro peptide F and FMRFamide-related peptides (FaRPs). Both families of neuropeptide are abundant and broadly distributed in platyhelminths, occurring in neuronal vesicles in representatives of all major flatworm taxa. Dual localization studies have revealed that peptidergic and cholinergic substances occupy neuronal sets separate from those of serotoninergic components. The physiological actions of neuronal messengers in flatworms are beginning to be established, and where examined, FaRPs and 5-HT are myoexcitatory, while cholinomimetic substances are generally inhibitory. There is immunocytochemical evidence that FaRPs and 5-HT have a regulatory role in the mechanism of egg assembly. Use of muscle strips and (or) muscle fibres from free-living and parasitic flatworms has provided baseline information to indicate that muscle responses to FaRPs are mediated by a G-protein-coupled receptor, and that the signal transduction pathway for contraction involves the second messengers cAMP and protein kinase C.

Clinical relevance of the neurotrophins and their receptors

2006 ◽  
Vol 110 (2) ◽  
pp. 175-191 ◽  
Author(s):  
Shelley J. Allen ◽  
David Dawbarn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Disease Process ◽  
Neuronal Cell ◽  
Cell Types ◽  
Dependent Manner ◽  
Disease States ◽  
Neuronal Tissues

The neurotrophins are growth factors required by discrete neuronal cell types for survival and maintenance, with a broad range of activities in the central and peripheral nervous system in the developing and adult mammal. This review examines their role in diverse disease states, including Alzheimer's disease, depression, pain and asthma. In addition, the role of BDNF (brain-derived neurotrophic factor) in synaptic plasticity and memory formation is discussed. Unlike the other neurotrophins, BDNF is secreted in an activity-dependent manner that allows the highly controlled release required for synaptic regulation. Evidence is discussed which shows that sequestration of NGF (nerve growth factor) is able to reverse symptoms of inflammatory pain and asthma in animal models. Both pain and asthma show an underlying pathophysiology linked to increases in endogenous NGF and subsequent NGF-dependent increase in BDNF. Conversely, in Alzheimer's disease, there is a role for NGF in the treatment of the disease and a recent clinical trial has shown benefit from its exogenous application. In addition, reductions in BDNF, and changes in the processing and usage of NGF, are evident and it is possible that both NGF and BDNF play a part in the aetiology of the disease process. This highly selective choice of functions and disease states related to neurotrophin function, although in no way comprehensive, illustrates the importance of the neurotrophins in the brain, the peripheral nervous system and in non-neuronal tissues. Ways in which the neurotrophins, their receptors or agonists/antagonists may act therapeutically are discussed.

Functional morphology of the platyhelminth nervous system

Parasitology ◽  
1996 ◽  
Vol 113 (S1) ◽  
pp. S47-S72 ◽  
Author(s):  
D. W. Halton ◽  
M. K. S. Gustafsson
Keyword(s):  
Nervous System ◽  
Sense Organ ◽  
Neuronal Cell ◽  
Cell Types ◽  
Target Cells ◽  
Life Styles ◽  
Wide Range ◽  
Paracrine Secretion ◽  
Nervous System Evolution ◽  
Neuronal Vesicles

SUMMARYAs the most primitive metazoan phylum, the Platyhelminthes occupies a unique position in nervous system evolution. Centrally, their nervous system consists of an archaic brain from which emanate one or more pairs of longitudinal nerve cords connected by commissures; peripherally, a diverse arrangement of nerve plexuses of varying complexity innervate the subsurface epithelial and muscle layers, and in the parasitic taxa they are most prominent in the musculature of the attachment organs and egg-forming apparatus. There is a range of neuronal-cell types, the majority being multi- and bipolar. The flatworm neuron is highly secretory and contains a heterogeneity of vesicular inclusions, dominated by densecored vesicles, whose contents may be released synaptically or by paracrine secretion for presumed delivery to target cells via the extracellular matrix. A wide range of sense organ types is present in flatworms, irrespective of life-styles. The repertoire of neuronal substances identified cytochemically includes all of the major candidate transmitters known in vertebrates. Two groups of native flatworm neuropeptides have been sequenced, neuropeptide F and FMRFamide-related peptides (FaRPs), and immunoreactivities for these have been localised in dense-cored neuronal vesicles in representatives of all major fiatworm groups. There is evidence of co-localisation of peptidergic and cholinergic elements; serotoninergic components generally occupy a separate set of neurons. The actions of neuronal substances in flatworms are largely undetermined, but FaRPs and 5-HT are known to be myoactive in all of the major groups, and there is immuno-cytochemical evidence that they have a role in the mechanism of egg assembly.

scholarly journals p53 Deficiency Rescues Neuronal Apoptosis but Not Differentiation in DNA Polymerase β-Deficient Mice

2004 ◽  
Vol 24 (21) ◽  
pp. 9470-9477 ◽  
Author(s):  
Noriyuki Sugo ◽  
Naoko Niimi ◽  
Yasuaki Aratani ◽  
Keiko Takiguchi-Hayashi ◽  
Hideki Koyama
Keyword(s):  
Nervous System ◽  
Dna Polymerase ◽  
Mammalian Cells ◽  
Neuronal Apoptosis ◽  
Excision Repair ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Types ◽  
Dna Polymerase Β ◽  
Deficient Mice

ABSTRACT In mammalian cells, DNA polymerase β (Polβ) functions in base excision repair. We have previously shown that Polβ-deficient mice exhibit extensive neuronal cell death (apoptosis) in the developing nervous system and that the mice die immediately after birth. Here, we studied potential roles in the phenotype for p53, which has been implicated in DNA damage sensing, cell cycle arrest, and apoptosis. We generated Polβ−/− p53−/− double-mutant mice and found that p53 deficiency dramatically rescued neuronal apoptosis associated with Polβ deficiency, indicating that p53 mediates the apoptotic process in the nervous system. Importantly, proliferation and early differentiation of neuronal progenitors in Polβ−/− p53−/− mice appeared normal, but their brains obviously displayed cytoarchitectural abnormalities; moreover, the mice, like Polβ−/− p53+/+ mice, failed to survive after birth. Thus, we strongly suggest a crucial role for Polβ in the differentiation of specific neuronal cell types.

scholarly journals Agrin Isoforms with Distinct Amino Termini

2000 ◽  
Vol 151 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Robert W. Burgess ◽  
William C. Skarnes ◽  
Joshua R. Sanes
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Subcellular Localization ◽  
Mouse Genome ◽  
Neuromuscular Junctions ◽  
Neuronal Cell ◽  
Cell Types ◽  
Detectable Effect ◽  
Neuromuscular Synaptogenesis

The proteoglycan agrin is required for postsynaptic differentiation at the skeletal neuromuscular junction, but is also associated with basal laminae in numerous other tissues, and with the surfaces of some neurons. Little is known about its roles at sites other than the neuromuscular junction, or about how its expression and subcellular localization are regulated in any tissue. Here we demonstrate that the murine agrin gene generates two proteins with different NH2 termini, and present evidence that these isoforms differ in subcellular localization, tissue distribution, and function. The two isoforms share ∼1,900 amino acids (aa) of common sequence following unique NH2 termini of 49 or 150 aa; we therefore call them short NH2-terminal (SN) and long NH2-terminal (LN) isoforms. In the mouse genome, LN-specific exons are upstream of an SN-specific exon, which is in turn upstream of common exons. LN-agrin is expressed in both neural and nonneural tissues. In spinal cord it is expressed in discrete subsets of cells, including motoneurons. In contrast, SN-agrin is selectively expressed in the nervous system but is widely distributed in many neuronal cell types. Both isoforms are externalized from cells but LN-agrin assembles into basal laminae whereas SN-agrin remains cell associated. Differential expression of the two isoforms appears to be transcriptionally regulated, whereas the unique SN and LN sequences direct their distinct subcellular localizations. Insertion of a “gene trap” construct into the mouse genome between the LN and SN exons abolished expression of LN-agrin with no detectable effect on expression levels of SN-agrin or on SN-agrin bioactivity in vitro. Agrin protein was absent from all basal laminae in mice lacking LN-agrin transcripts. The formation of the neuromuscular junctions was as drastically impaired in these mutants as in mice lacking all forms of agrin. Thus, basal lamina–associated LN-agrin is required for neuromuscular synaptogenesis, whereas cell-associated SN-agrin may play distinct roles in the central nervous system.

scholarly journals Vinaxanthone inhibits Semaphorin3A induced axonal growth cone collapse in embryonic neurons but fails to block its growth promoting effects on adult neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Evguenia Ivakhnitskaia ◽  
Matthew R. Chin ◽  
Dionicio Siegel ◽  
Victor H. Guaiquil
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Neuronal Cell ◽  
Neurite Growth ◽  
Cell Types ◽  
Pleiotropic Effect ◽  
In Vivo Models ◽  
Peripheral Neurons ◽  
Growth Cone Collapse

AbstractSemaphorin3A is considered a classical repellent molecule for developing neurons and a potent inhibitor of regeneration after nervous system trauma. Vinaxanthone and other Sema3A inhibitors are currently being tested as possible therapeutics to promote nervous system regeneration from injury. Our previous study on Sema3A demonstrated a switch in Sema3A’s function toward induction of nerve regeneration in adult murine corneas and in culture of adult peripheral neurons. The aim of the current study is to determine the direct effects of Vinaxanthone on the Sema3A induced adult neuronal growth. We first demonstrate that Vinaxanthone maintains its anti-Sema3A activity in embryonic dorsal root ganglia neurons by inhibiting Sema3A-induced growth cone collapse. However, at concentrations approximating its IC50 Vinaxanthone treatment does not significantly inhibit neurite formation of adult peripheral neurons induced by Sema3A treatment. Furthermore, Vinaxanthone has off target effects when used at concentrations above its IC50, and inhibits neurite growth of adult neurons treated with either Sema3A or NGF. Our results suggest that Vinaxanthone’s pro-regenerative effects seen in multiple in vivo models of neuronal injury in adult animals need further investigation due to the pleiotropic effect of Sema3A on various non-neuronal cell types and the possible effect of Vinaxanthone on other neuroregenerative signals.

scholarly journals GABAergic Neuron Specification in the Spinal Cord, the Cerebellum, and the Cochlear Nucleus

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kei Hori ◽  
Mikio Hoshino
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Cochlear Nucleus ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Lineage Tracing ◽  
Inhibitory Neurons ◽  
Genetic Lineage ◽  
Genetic Lineage Tracing

In the nervous system, there are a wide variety of neuronal cell types that have morphologically, physiologically, and histochemically different characteristics. These various types of neurons can be classified into two groups: excitatory and inhibitory neurons. The elaborate balance of the activities of the two types is very important to elicit higher brain function, because its imbalance may cause neurological disorders, such as epilepsy and hyperalgesia. In the central nervous system, inhibitory neurons are mainly represented by GABAergic ones with some exceptions such as glycinergic. Although the machinery to specify GABAergic neurons was first studied in the telencephalon, identification of key molecules, such as pancreatic transcription factor 1a (Ptf1a), as well as recently developed genetic lineage-tracing methods led to the better understanding of GABAergic specification in other brain regions, such as the spinal cord, the cerebellum, and the cochlear nucleus.

scholarly journals The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Stephanie M. Boas ◽  
Kathlene L. Joyce ◽  
Rita M. Cowell
Keyword(s):  
Oxidative Stress ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Cellular Localization ◽  
Family Members ◽  
Neuronal Cell ◽  
Cell Types ◽  
Antioxidant Defenses ◽  
Cell Type Specific ◽  
Specific Vulnerability

Oxidative stress has been implicated in the etiology and pathobiology of various neurodegenerative diseases. At baseline, the cells of the nervous system have the capability to regulate the genes for antioxidant defenses by engaging nuclear factor erythroid 2 (NFE2/NRF)-dependent transcriptional mechanisms, and a number of strategies have been proposed to activate these pathways to promote neuroprotection. Here, we briefly review the biology of the transcription factors of the NFE2/NRF family in the brain and provide evidence for the differential cellular localization of NFE2/NRF family members in the cells of the nervous system. We then discuss these findings in the context of the oxidative stress observed in two neurodegenerative diseases, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), and present current strategies for activating NFE2/NRF-dependent transcription. Based on the expression of the NFE2/NRF family members in restricted populations of neurons and glia, we propose that, when designing strategies to engage these pathways for neuroprotection, the relative contributions of neuronal and non-neuronal cell types to the overall oxidative state of tissue should be considered, as well as the cell types which have the greatest intrinsic capacity for producing antioxidant enzymes.

scholarly journals The molecular underpinnings of neuronal cell identity in the stomatogastric ganglion of cancer borealis

2019 ◽  
Author(s):  
◽  
Adam Jared Northcutt
Keyword(s):  
Nervous System ◽  
Ion Channel ◽  
Transcriptome Assembly ◽  
Neuronal Cell ◽  
Cell Types ◽  
Molecular Profile ◽  
Receptor Subtypes ◽  
Stomatogastric Nervous System ◽  
Cancer Borealis ◽  
Cell Identity

Throughout the life of an organism, the nervous system must be able to balance changing in response to environmental stimuli with the need to produce reliable, repeatable activity patterns to create stereotyped behaviors. Understanding the mechanisms responsible for this regulation requires a wealth of knowledge about the neural system, ranging from network connectivity and cell type identification to intrinsic neuronal excitability and transcriptomic expression. To make strides in this area, we have employed the well-described stomatogastric nervous system of the Jonah crab Cancer borealis to examine the molecular underpinnings and regulation of neuron cell identity. Several crustacean circuits, including the stomatogastric nervous system and the cardiac ganglion, continue to provide important new insights into circuit dynamics and modulation (Diehl, White, Stein, and Nusbaum, 2013; Marder, 2012; Marder and Bucher, 2007; Williams et al., 2013), but this work has been partially hampered by the lack of extensive molecular sequence knowledge in crustaceans. Here we generated de novo transcriptome assembly from central nervous system tissue for C. borealis producing 42,766 contigs, focusing on an initial identification, curation, and comparison of genes that will have the most profound impact on our understanding of circuit function in these species. This included genes for 34 distinct ion channel types, 17 biogenic amine and 5 GABA receptors, 28 major transmitter receptor subtypes including glutamate and acetylcholine receptors, and 6 gap junction proteins -- the Innexins. ... With this reference transcriptome and annotated sequences in hand, we sought to determine the strengths and limitations of using the neuronal molecular profile to classify them into cell types. ... Since the resulting activity of a neuron is the product of the expression of ion channel genes, we sought to further probe the expression profile of neurons across a range of cell types to understand how these patterns of mRNA abundance relate to the properties of individual cell types. ... Finally, we sought to better understand the molecular underpinnings of how these correlated patterns of mRNA expression are generated and maintained.

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