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PubMed2006

Immunoreactivities to protein gene product 9.5, neurofilament protein and neuron specific enolase in nerves in the oviduct of the sexually immature ostrich, Struthio camelus.

The present study investigated the distribution of nerves in the oviduct of the sexually immature ostrich. The presence of protein gene product 9.5, neurofilament protein and neuron specific enolase nerve fibres were demonstrated in the infundibulum, magnum, isthmus, shell gland and vagina. Nerve fibres containing protein gene product 9.5, neuron specific enolase and neurofilament protein were particularly numerous in the tunica muscularis and intermuscular connective tissue areas of the shell gland and vagina. The presence of a large number of nerves in these oviductal regions is probably important in the coordination of muscle contraction. An interesting finding of the study was the presence of protein gene product 9.5 and neuron specific enolase immunopositive nerve fibres in the walls of blood vessels. It is likely that these nerves are autonomicin nature and play a role in the regulation of blood flow. This study has shown the presence of an extensive neural network in the oviduct of the ostrich. In addition, the results of the investigation have shown that the neuronal markers protein gene product 9.5, neurofilament protein and neuron specific enolase can be used to demonstate nerve fibres in the ostrich.

Animals↗
PubMed1997

Immunohistochemical localization of the neuron-specific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody.

Neuronal regulation of glutamate homeostasis is mediated by high-affinity sodium-dependent and highly hydrophobic plasma membrane glycoproteins which maintain low levels of glutamate at central synapses. To further elucidate the molecular mechanisms that regulate glutamate metabolism and glutamate flux at central synapses, a monoclonal antibody was produced to a synthetic peptide corresponding to amino acid residues 161-177 of the deduced sequence of the human neuron-specific glutamate transporter III (EAAC1). Immunoblot analysis of human and rat brain total homogenates and isolated synaptosomes from frontal cortex revealed that the antibody immunoreacted with a protein band of apparent Mr approximately 70 kDa. Deglycosylation of immunoprecipitates obtained using the monoclonal antibody yielded a protein with a lower apparent Mr (approximately 65 kDa). These results are consistent with the molecular size of the human EAAC1 predicted from the cloned cDNA. Analysis of the transfected COS-1 cells by immunocytochemistry confirmed that the monoclonal antibody is specific for the neuron-specific glutamate transporter. Immunocytochemical studies of rat cerebral cortex, hippocampus, cerebellum, substantia nigra and spinal cord revealed intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta. Double-label immunofluorescence using antibody to glial fibrillary acidic protein as a marker for astrocytes demonstrated that astrocytes were not co-labeled for EAAC1. The localization of EAAC1 immunoreactivity in dendrites and particularly in cell somata suggests that this transporter may function in the regulation of other aspects of glutamate metabolism in addition to terminating the action of synaptically released glutamate at central synapses.

Adult↗
PubMedDate not supplied

Neuron-specific monoclonal antibodies raised against the low molecular weight fraction of a brain homogenate of the pond snail Lymnaea stagnalis immunoreact with neurons in the central nervous system of the cockroach, the guppy, the wall lizard, the rat and man.

Monoclonal antibodies were raised against the small molecular weight fraction (less than 30 kilodaltons) of an extract from 200 central nervous systems (CNS) of the freshwater snail Lymnaea stagnalis. In a first screening step the supernatants of the 297 emerging hybridomas were immunocytochemically tested on sections of the CNS of L. stagnalis. Sixty-six appeared to produce neuron-specific antibodies, five reacted with non-neuronal elements. In a second step the 66 neuron-specific antibodies were tested on sections of the CNS of the guppy. Three reacted positively. In the third step the three antibodies were tested on the CNS of the rat. One antibody (Mab4H5) appeared to give positive results. In the snail brain Mab4H5 stains two identified giant neurons, one in the visceral ganglion (VD1), and one in the right parietal ganglion (RPD2)--these neurons form part of the network controlling the respiratory system--and a small number of cells in the cerebral ganglia (in the anterior and ventral lobes). Ultrastructural observations using immunogold labelling in VD1 showed the antigen to be localized to the secretory vesicles. In the guppy Mab4H5 stains fibres in the tectum and cell bodies in the reticular formation. In rat CNS staining was observed in Purkinje neurons of the cerebellum, in cortical pyramidal neurons and in neurons and fibres in other brain areas. Subsequent Mab4H5 staining of the CNS of the lizard, the cockroach and parts of the human CNS showed that these tissues also contain Mab4H5-positive neurons. In the human cortex and cerebellum the staining pattern appeared to be similar to that of the rat. On the basis of the results it is hypothesized that the antibody reacts with phylogenetically ancient amino acid sequences.

Animals↗
PubMed1990

Human chorionic gonadotropin, neuron specific enolase and deoxyribonucleic acid flow cytometry in patients with high grade bladder carcinoma.

Biopsies from 64 patients with transitional cell carcinoma of the bladder (World Health Organization grade 3 and undifferentiated) were studied with deoxyribonucleic acid flow cytometry of fresh tissue and immunohistochemical staining on the histopathological slides for the presence of neuron specific enolase and human chorionic gonadotropin. No correlation was found among the presence of neuron specific enolase or human chorionic gonadotropin and T category, deoxyribonucleic acid ploidy, percentage of cells in the S phase, presence of metastatic disease or response to therapy. The prognosis for patients with muscle invasive disease and tumors positive for neuron specific enolase or human chorionic gonadotropin was similar to that for patients with tumors negative for these substances. When a possible new marker or prognostic factor is evaluated, it is important to investigate whether the new marker adds information on prognosis to what already is known by established standard methods. Further studies are needed to evaluate the clinical importance of human chorionic gonadotropin (and neuron specific enolase) as a marker in urothelial cancer with regard to prognosis and response to therapy.

Biomarkers, Tumor↗
PubMed2003

Frequency-specific interaural level difference tuning predicts spatial response patterns of space-specific neurons in the barn owl inferior colliculus.

Space-specific neurons in the barn owl's inferior colliculus have spatial receptive fields (RFs) because of sensitivity to interaural time difference and frequency-specific interaural level difference (ILD). These neurons are assumed to be tuned to the frequency-specific ILDs occurring at their spatial RFs, but attempts to assess this tuning with traditional narrowband stimuli have had limited success. Indeed, tuning assessed in this manner, when processed via a linear model of spectral integration, typically explains only approximately half the variance in spatial response patterns. Here we report our findings that frequency-specific ILD tuning of space-specific neurons, when assessed from responses to broadband stimuli, predicted nearly 75% of the variance in spatial responses, using a linear model of spectral integration (p < 0.0001; n = 97 neurons). Furthermore, when we tested neurons using only those frequencies we found to be spatially relevant, we saw that their responses were similar to those elicited by broadband stimuli. When we used frequencies not identified as spatially relevant, such similarity was lacking. Furthermore, spectral components that elicited high firing rates when presented as narrowband stimuli were found in several cases to be irrelevant for or detrimental to the definition of spatial RFs. Thus, neurons achieved sharp spatial tuning by selecting for ILDs of a subset of spectral components in noise, some of which were not identified using narrowband stimuli.

Acoustic Stimulation↗
PubMed1998

Non increased neuron-specific enolase concentration in cerebrospinal fluid during first febrile seizures and a year follow-up in pediatric patients.

Febrile seizures are the commonest acute neurological disorder of early childhood. Studies suggested that febrile seizures are previous acute events from a more serious neurological problem. Due to neuron-specific enolase is generally accepted as a marker for neuropathological processes in the brain, 16 pediatric patients were studied during their first seizures and a year after it. Neuron-specific enolase in cerebrospinal fluid and blood were analysed by an immune enzyme assay. Non pathological neuron-specific enolase values were obtained in both periods in the group of patients. There were no significative differences when paired series statistics test was performed with 95% of confidence. Neuron-specific enolase appears not to be a marker for febrile seizures because its concentration not be increased in cerebrospinal fluid in this group of patients.

Cerebrospinal Fluid↗
PubMed1984

Neuron-specific phosphoproteins as biochemical indicators of neurotoxicity: effects of acute administration of trimethyltin to the adult rat.

The cytoarchitecture of the adult central nervous system is expressed by proteins specific to individual cell types. In this investigation, a subclass of these proteins, the neuron-specific phosphoproteins, was examined after the administration of trimethyltin (TMT), a neurotoxicant which preferentially damages neurons in limbic structures. After acute administration of TMT (0.0-9.0 mg/kg i.v.), effects on neuronal phosphoproteins were examined by three separate techniques: endogenous phosphorylation of total synaptic membrane proteins; radiometric assay of synapsin I, a neuron-specific phosphoprotein associated with synaptic vesicles; and radioimmunoassay of synapsin I and protein III, another synapse specific, synaptic vesicle-localized phosphoprotein. All three procedures gave similar results. TMT caused dose- and time-dependent decreases in hippocampal phosphoproteins. These effects were large in magnitude and were still evident 14 weeks after exposure to TMT. Microdissection of slices of dorsal hippocampus did not reveal significant regional differences in the extent to which TMT affected synapsin I. Phosphoproteins in frontal cortex, unlike those in hippocampus, were not affected by TMT. Our findings are consistent with the neuropathological effects of this compound and suggest that neuron-specific phosphoproteins may be useful biochemical indicators of neurotoxicity.

Animals↗
PubMed1999

Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat.

Neuron-restrictive silencer factor (NRSF), also known as repressor element RE1 binding transcription factor (REST) or repressor binding to the X2 box (XBR) (REST/NRSF/XBR), is a zinc finger transcription factor that during early embryogenesis is required to repress a subset of neuron-specific genes in non-neural tissues and undifferentiated neural precursors. We have previously shown that splicing within the coding region of rat REST/NRSF/XBR (rREST) generates several different transcripts all of which are expressed in the adult nervous system. rREST transcripts with short neuron-specific exons (exon N) have in-frame stop codons and encode truncated proteins which have an N-terminal repressor domain and weakened DNA binding activity. The aim of this study was to analyze the regulatory mechanisms underlying REST/NRSF/XBR activity in human and mouse as compared to rat. We show that the structure of REST/NRSF/XBR gene and its regulation by neuron-specific splicing is conserved in human, mouse and rat. Expression levels of REST/NRSF/XBR transcripts with the insertion of exon N are increased during the neuronal differentiation of mouse teratocarcinoma PCC7 and rat pheocromocytoma PC12 cells and are high in several human and mouse neuroblastoma cells as compared to the relatively low levels in the developing and adult nervous system. The exclusive expression of the neuronal forms of REST/NRSF/XBR mRNAs in mouse neuroblastoma Neuro-2A cells is not caused by rearrangement of the REST/NRSF/XBR gene nor by mutations in the sequence of the splice sites flanking exon N. These data suggest that changes in REST/NRSF/XBR splicing pattern may result from altered levels of splicing factors reflecting the formation and/or progression of neuroblastoma tumors.

Animals↗
PubMed1982

Synapse formation is related to the onset of neuron-specific enolase immunoreactivity in the avian auditory and vestibular systems.

Neuron-specific enolase (NSE) is a unique form of the glycolytic enzyme, enolase, which, in the brain, is strictly localized in differentiated neurons and neuroendocrine cells. In this report evidence is presented that NSE is first seen in the cell bodies of developing chick auditory and vestibular neurons shortly after the time when they first form immature synapses. Subsequently, immunoreactive NSE increases and spreads into transiently appearing structures which participate in the morphogenesis of mature synaptic arrangements. These data correlate synaptogenesis with the differentiation of a specific neuronal enzyme.

Animals↗
PubMed1984

Experimental brain ischemia: neuron-specific enolase level in cerebrospinal fluid as an index of neuronal damage.

Levels of neuron-specific enolase (NSE) were measured in rat CSF following occlusion of the four major arteries to the brain for 10, 20, or 30 min. In the CSF of rats submitted to 30 min of total ischemia, an up to nine-fold increase of NSE level occurred within the first few hours and then slowly diminished. Significant levels were seen for as long as 8 days. Histological observations 3 days after ischemia showed neuronal loss as well as neuronal damage in several forebrain regions such as hippocampus, striatum, and thalamus. Ischemia was followed by transient decreases in exploration behavior and neurological states that were no longer visible 24 h later. After 10 or 20 min ischemia, NSE levels were increased to a lesser degree and fewer damaged neurons were observed. The positive correlation between duration of ischemia and amount of NSE release in CSF indicates that the measurement of NSE in the CSF is a sensitive and reliable index of neuronal lesions.

Animals↗
PubMed1998

Multiple factors interacting at the GATA sites of the gonadotropin-releasing hormone neuron-specific enhancer regulate gene expression.

Neuron-specific expression of the GnRH gene is dependent on an upstream multicomponent enhancer. This enhancer is functional in a small population of GnRH-producing hypothalamic neurons which, through the secretion of GnRH, mediates central nervous system control of reproductive function. GnRH enhancer function requires activation by the GATA family of transcription factors that act through tandem consensus GATA-binding motifs, GATA-A and GATA-B. Here we show that two newly identified DNA-binding factors, termed GBF-A1/A2 and GBF-B1, bind the GnRH enhancer at sites overlapping the GATA factor-binding motifs. In vitro bindings of GATA, GBF-A1/A2, and GBF-B1 to the GnRH enhancer sequences are independent. Specific mutation of either the consensus GATA motif or the GBF-B1 site of GATA-B does not alter binding of the overlapping factor in vitro. Utilizing a GnRH-expressing neuronal cell line as a model system, we show by transient transfection that GBF-B1 is necessary for enhancer activity and independently activates the GnRH promoter. Transactivation of the GnRH enhancer in GT1 cells and in NIH 3T3 cells by GATA-4 is modulated by GBF-B1 binding, suggesting GBF-B1 interferes with GATA factor binding through a steric mechanism.

Animals↗
PubMed1984

Neuron-specific enolase in the diagnosis of neuroblastoma and other small, round-cell tumors in children.

Immunocytochemical staining for neuron-specific enolase (NSE) was performed in 44 round-cell tumors from children by the improved immunoglobulin-enzyme bridge method with antiserum against NSE. The tumors studied consisted of 15 neuroblastomas showing various degrees of histologic differentiation, 13 Ewing's sarcomas, ten soft tissue sarcomas of diverse origin, and six lymphomas of bone and soft tissues. Neuron-specific enolase was detected in all neuroblastomas, irrespective of the degree of histologic differentiation. None of the other round-cell tumors was positive for NSE, except one embryonal rhabdomyosarcoma that contained differentiated myoblasts. The primitive cells of this tumor were negative as well. It is concluded that immunocytochemical staining with antibodies to NSE is a practical and reliable method for distinguishing neuroblastomas from other nonneural round-cell tumors in children. This is true even for the most primitive forms of neuroblastomas, in which morphologic techniques are less reliable. Neuron-specific enolase may also be useful in delineating the neural histogenesis of other ill-defined tumors.

Adult↗
PubMed2005

The C. elegans nuclear receptor gene fax-1 and homeobox gene unc-42 coordinate interneuron identity by regulating the expression of glutamate receptor subunits and other neuron-specific genes.

The fax-1 gene of the nematode C. elegans encodes a conserved nuclear receptor that is the ortholog of the human PNR gene and functions in the specification of neuron identities. Mutations in fax-1 result in locomotion defects. FAX-1 protein accumulates in the nuclei of 18 neurons, among them the AVA, AVB, and AVE interneuron pairs that coordinate body movements. The identities of AVA and AVE interneurons are defective in fax-1 mutants; neither neuron expresses the NMDA receptor subunits nmr-1 and nmr-2. Other ionotropic glutamate receptor subunits are expressed normally in the AVA and AVE neurons. The unc-42 homeobox gene also regulates AVA and AVE identity; however, unc-42 mutants display the complementary phenotype: NMDA receptor subunit expression is normal, but some non-NMDA glutamate receptor subunits are not expressed. These observations support a combinatorial role for fax-1 and unc-42 in specifying AVA and AVE identity. However, in four other neuron types, fax-1 is regulated by unc-42, and both transcriptional regulators function in the regulation of the opt-3 gene in the AVE neurons and the flp-1 and ncs-1 genes in the AVK neurons. Therefore, while fax-1 and unc-42 act in complementary parallel pathways in some cells, they function in overlapping or linear pathways in other cellular contexts, suggesting that combinatorial relationships among transcriptional regulators are complex and cannot be generalized from one neuron type to another.

Animals↗
PubMed1982

Reduction of neuronal specific protein and some neurotransmitters in the infantile neuroaxonal dystrophy (INAD).

INAD with classical clinicopathological features was seen in three children of one family. They presented with a history of regression after the age of 1.5 years and died in mental institutions at the ages of 6, 7 and 9. Two of them had postmortem neuropathological studies, one had brain biopsy and one biochemical study. The following observations have been made; I. Histological--(1) some axonal loss with almost total absence of neurofilaments in dystrophic neurites and (2) marked degenerative changes and loss of synaptic vesicles; II. Biochemical--(1) the decrease of the neurofilament polypeptides by up to 75% and (2) a reduction of some neurotransmitter enzymes. The presence of intermitochondrial septate junctions. The neurofilament protein is specific to neurons and makes up a large percentage of their protein content. Neurofilaments have been implicated in several cellular functions such as intracellular transport and in the maintenance of cell structure. The decrease of neurofilament protein in our case is compatible with our morphological findings where we found decreased numbers of axons and an almost total absence of neurofilaments in the affected neurites.

Axons↗
PubMed2006

Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial DNA defects.

Maintenance of mitochondrial DNA (mtDNA) depends on nuclear-encoded proteins such as mtDNA polymerase (POLG), whose mutations are involved in the diseases caused by mtDNA defects including mutation and deletion. The defects in mtDNA and in intracellular Ca2+ ([Ca2+]i) homeostasis have been reported in bipolar disorder (BD). To understand the relevance of the mtDNA defects to BD, we studied transgenic (Tg) mice in which mutant POLG (mutPOLG) was expressed specifically in neurons. mtDNA defects were accumulated in the brains of mutPOLG Tg mice in an age-dependent manner and the mutant mice showed BD-like behavior. However, the molecular and cellular basis for the abnormalities has not been clarified. In this study, we investigated Ca2+ regulation by isolated mitochondria and [Ca2+]i dynamics in the neurons of mutPOLG Tg mice. Mitochondria from the mutant mice sequestered Ca2+ more rapidly, whereas Ca2+ retention capacity and membrane potential, a driving force of Ca2+ uptake, of mitochondria were unaffected. To elucidate the molecular mechanism of the altered Ca2+ uptake, we performed DNA microarray analysis and found that the expression of cyclophilin D (CyP-D), a component of the permeability transition pore, was downregulated in the brains of mutPOLG Tg mice. Cyclosporin A, an inhibitor of CyP-D, mimicked the enhanced Ca2+ uptake in mutant mice. Furthermore, G-protein-coupled receptor-mediated [Ca2+]i increase was attenuated in hippocampal neurons of the mutant mice. These findings suggest that mtDNA defects lead to enhancement of Ca2+ uptake rate via CyP-D downregulation and alter [Ca2+]i dynamics, which may be involved in the pathogenesis of BD.

Age Factors↗
PubMed2006

A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators.

Recent advances in genome-wide analysis of alternative splicing indicate that extensive alternative RNA processing is associated with many proteins that play important roles in the nervous system. Although differential splicing and polyadenylation make significant contributions to the complexity of the nervous system, our understanding of the regulatory mechanisms underlying the neuron-specific pathways is very limited. Mammalian neuron-specific embryonic lethal abnormal visual-like Hu proteins (HuB, HuC, and HuD) are a family of RNA-binding proteins implicated in neuronal differentiation and maintenance. It has been established that Hu proteins increase expression of proteins associated with neuronal function by up-regulating mRNA stability and/or translation in the cytoplasm. We report here a novel function of these proteins as RNA processing regulators in the nucleus. We further elucidate the underlying mechanism of this regulation. We show that in neuron-like cells, Hu proteins block the activity of TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA processing. These studies define not only the first neuron-specific regulator of the calcitonin/CGRP system but also the first nuclear function of Hu proteins.

Alternative Splicing↗
PubMed2003

Release of neuron-specific enolase and S100 after implantation of cardioverters/defibrillators.

OBJECTIVE: Repeated induction of ventricular fibrillation with ensuing alterations in electroencephalogram and jugular venous oxygen saturation is common practice during insertion of transvenous implantable cardioverters/defibrillators. We investigated whether these functional changes are also associated with cerebral injury. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: We studied 45 patients undergoing implantable cardioverter/defibrillator insertion. Eleven patients with cardiac pacemaker implantation, which was performed in the same manner yet without the necessity to induce ventricular fibrillation, served as controls. MEASUREMENTS AND MAIN RESULTS: Serum neuron-specific enolase and S100 were determined before, immediately postoperatively, and 2 hrs postoperatively. In a randomly composed subgroup, neuron-specific enolase was also determined 6 and 24 hrs after surgery. Implantable cardioverter/defibrillator patients only showed an increase of both markers postoperatively. Median neuron-specific enolase values climbed from a preoperative 9.9 to 12.3 and 14.4 microg/L at 2 and 24 hrs after surgery, respectively. This increase was associated with the number of shocks and the cumulative time in circulatory arrest. The highest median S100 level (0.075 microg/L) was reached 2 hrs after the procedure. Neuron-specific enolase and S100 were extremely elevated (13.7 and 0.970 microg/L, respectively) in one patient after an extended episode of ventricular fibrillation. Plasma hemoglobin levels were in the normal range in implantable cardioverter/defibrillator patients throughout the observation period. CONCLUSIONS: Apparently, even brief successive periods of global cerebral ischemia cause neuronal damage without obvious severe neurologic deficits. However, they may be related to subtle postoperative neurologic or cognitive dysfunctions that a number of implantable cardioverter/defibrillator patients exhibit after implantation.

Aged↗