NeuN, a neuronal specific nuclear protein in vertebrates

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 201-211 ◽  
Author(s):  
R.J. Mullen ◽  
C.R. Buck ◽  
A.M. Smith
Keyword(s):  
Nervous System ◽  
Nuclear Protein ◽  
Neuronal Cell ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Brain Cell ◽  
Cell Nuclei ◽  
Neuronal Nuclei ◽  
Specific Nuclear Protein

A battery of monoclonal antibodies (mAbs) against brain cell nuclei has been generated by repeated immunizations. One of these, mAb A60, recognizes a vertebrate nervous system- and neuron-specific nuclear protein that we have named NeuN (Neuronal Nuclei). The expression of NeuN is observed in most neuronal cell types throughout the nervous system of adult mice. However, some major cell types appear devoid of immunoreactivity including cerebellar Purkinje cells, olfactory bulb mitral cells, and retinal photoreceptor cells. NeuN can also be detected in neurons in primary cerebellar cultures and in retinoic acid-stimulated P19 embryonal carcinoma cells. Immunohistochemically detectable NeuN protein first appears at developmental timepoints which correspond with the withdrawal of the neuron from the cell cycle and/or with the initiation of terminal differentiation of the neuron. NeuN is a soluble nuclear protein, appears as 3 bands (46-48 × 10(3) M(r)) on immunoblots, and binds to DNA in vitro. The mAb crossreacts immunohistochemically with nervous tissue from rats, chicks, humans, and salamanders. This mAb and the protein recognized by it serve as an excellent marker for neurons in the central and peripheral nervous systems in both the embryo and adult, and the protein may be important in the determination of neuronal phenotype.

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 An investigation of acid-soluble nuclear proteins of human leucocytes in relation to fraction RP2-L, a component of neoplastic cells

1968 ◽  
Vol 107 (6) ◽  
pp. 799-806 ◽  
Author(s):  
A J MacGillivray ◽  
J. P. P. V. Monjardino
Keyword(s):  
Nuclear Protein ◽  
Tumour Cells ◽  
Nuclear Proteins ◽  
Cell Nuclei ◽  
Histone Protein ◽  
Chromosomal Origin ◽  
Nuclear Extracts ◽  
Mixed Samples ◽  
Specific Nuclear Protein

1. The claim that tumour cells contain a specific nuclear protein was investigated. The presence of this component was confirmed in Walker tumour cells by the chromatography on CM-cellulose of nuclear proteins labelled with [14C]lysine. This protein was studied further in a number of human leucocyte cells. 2. The labelling of leucocyte nuclear proteins with [14C]lysine was attempted during incubation and culture in vitro. Incorporation of the label into acid-soluble nuclear proteins was highest in normal lymphocytes cultured with phytohaemagglutinin, followed by chronic-myeloid-leukaemic leucocytes and mixed samples of normal leucocytes incubated in plasma. Little incorporation was seen in similar extracts of chronic-lymphatic or normal leucocytes. 3. Lymphocytes were the only cells that gave nuclear extracts with amino acid analysis similar to that of unfractionated histones. 4. Little of the [14C]lysine in nuclear extracts of incubated leucocytes proved to be of chromosomal origin. No evidence was found of an RP2-L component in the highly labelled nuclear extracts of phytohaemagglutinin-treated lymphocytes until after 6 days of culture with [14C]lysine. This component was soluble in saline. 5. Evidence is presented that fraction RP2-L is a non-histone protein constituent of cell nuclei whose labelling with [14C]lysine may be dependent on the metabolic state of the cell. Thus this component is not specific to the neoplastic state.

scholarly journals Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Verena Schultz ◽  
Stephanie L. Cumberworth ◽  
Quan Gu ◽  
Natasha Johnson ◽  
Claire L. Donald ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Development ◽  
Zika Virus ◽  
Developmental Stages ◽  
Cell Types ◽  
Neural Cells ◽  
Zikv Infection ◽  
Axonal Pathology ◽  
Time Frames

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.

scholarly journals Cell type resolved co-expression networks of core clock genes in brain development

2021 ◽  
Author(s):  
Surbhi Sharma ◽  
Asgar Hussain Ansari ◽  
Soundhar Ramasamy
Keyword(s):  
Circadian Clock ◽  
Single Cell ◽  
Radial Glia ◽  
Clock Genes ◽  
Neuronal Cell ◽  
Cell Types ◽  
Developing Brain ◽  
Knock Out

AbstractThe circadian clock regulates vital cellular processes by adjusting the physiology of the organism to daily changes in the environment. Rhythmic transcription of core Clock Genes (CGs) and their targets regulate these processes at the cellular level. Circadian clock disruption has been observed in people with neurodegenerative disorders like Alzheimer’s and Parkinson’s. Also, ablation of CGs during development has been shown to affect neurogenesis in both in vivo and in vitro models. Previous studies on the function of CGs in the brain have used knock-out models of a few CGs. However, a complete catalog of CGs in different cell types of the developing brain is not available and it is also tedious to obtain. Recent advancements in single-cell RNA sequencing (scRNA-seq) has revealed novel cell types and elusive dynamic cell states of the developing brain. In this study by using publicly available single-cell transcriptome datasets we systematically explored CGs-coexpressing networks (CGs-CNs) during embryonic and adult neurogenesis. Our meta-analysis reveals CGs-CNs in human embryonic radial glia, neurons and also in lesser studied non-neuronal cell types of the developing brain.

scholarly journals Mitochondrial Calcium Uptake Capacity Modulates Neocortical Excitability

2013 ◽  
Vol 33 (7) ◽  
pp. 1115-1126 ◽  
Author(s):  
Basavaraju G Sanganahalli ◽  
Peter Herman ◽  
Fahmeed Hyder ◽  
Sridhar S Kannurpatti
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Types ◽  
Dependent Manner ◽  
Evoked Responses ◽  
Blood Oxygen Level ◽  
Calcium Uniporter ◽  
Sensory Evoked

Local calcium (Ca2 +) changes regulate central nervous system metabolism and communication integrated by subcellular processes including mitochondrial Ca2 + uptake. Mitochondria take up Ca2 + through the calcium uniporter (mCU) aided by cytoplasmic microdomains of high Ca2 +. Known only in vitro, the in vivo impact of mCU activity may reveal Ca2 + -mediated roles of mitochondria in brain signaling and metabolism. From in vitro studies of mitochondrial Ca2 + sequestration and cycling in various cell types of the central nervous system, we evaluated ranges of spontaneous and activity-induced Ca2 + distributions in multiple subcellular compartments in vivo. We hypothesized that inhibiting (or enhancing) mCU activity would attenuate (or augment) cortical neuronal activity as well as activity-induced hemodynamic responses in an overall cytoplasmic and mitochondrial Ca2 + -dependent manner. Spontaneous and sensory-evoked cortical activities were measured by extracellular electrophysiology complemented with dynamic mapping of blood oxygen level dependence and cerebral blood flow. Calcium uniporter activity was inhibited and enhanced pharmacologically, and its impact on the multimodal measures were analyzed in an integrated manner. Ru360, an mCU inhibitor, reduced all stimulus-evoked responses, whereas Kaempferol, an mCU enhancer, augmented all evoked responses. Collectively, the results confirm aforementioned hypotheses and support the Ca2 + uptake-mediated integrative role of in vivo mitochondria on neocortical activity.

scholarly journals Virulent and attenuated canine distemper virus infects multiple dog brain cell types in vitro

Glia ◽  
1991 ◽  
Vol 4 (4) ◽  
pp. 408-416 ◽  
Author(s):  
Susan Pearce-Kelling ◽  
William J. Mitchell ◽  
Brian A. Summers ◽  
Max J. G. Appel
Keyword(s):  
Canine Distemper Virus ◽  
Cell Types ◽  
Brain Cell ◽  
Canine Distemper ◽  
Dog Brain ◽  
Brain Cell Types

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 In vitro models for neurotoxicology research

2015 ◽  
Vol 4 (4) ◽  
pp. 801-842 ◽  
Author(s):  
Daniel José Barbosa ◽  
João Paulo Capela ◽  
Maria de Lourdes Bastos ◽  
Félix Carvalho
Keyword(s):  
Nervous System ◽  
Cell Types ◽  
In Vitro Models ◽  
Functional Characteristics ◽  
Multiple Functions ◽  
Complex Organization

The nervous system has a highly complex organization, including many cell types with multiple functions, with an intricate anatomy and unique structural and functional characteristics; the study of its (dys)functionality following exposure to xenobiotics, neurotoxicology, constitutes an important issue in neurosciences.

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