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PubMed1993

Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia.

Neuron-specific enolase (NSE) is an isoform of the glycolytic enzyme, enolase, and is found in neurons and neuroendocrine cells. We evaluated cerebral immunohistologic and plasma changes in NSE in rats from 2 h to 15 days following permanent or transient middle cerebral artery occlusion (MCAO). At 1-2 days post-MCAO, loss of NSE immunofluorescence from within neurons to the extracellular space was observed in the infarcted areas of all MCAO animals. NSE also was identified intravascularly throughout the brain following MCAO. NSE in plasma was determined by a specific radioimmunoassay. Plasma NSE following permanent or transient MCAO was increased significantly from that observed in controls (2.8 +/- 0.3 ng/ml) beginning at 2 h and persisting for 2.5 days post-MCAO (maximum levels of 8.8 +/- 0.9 to 9.6 +/- 0.5 ng/ml after 6-12 h; P < 0.05, n = 4-9). Quantified contralateral forelimb and hindlimb neurological deficits in these animals were significant and persisted for at least 15 days following MCAO but were not observed following sham surgery. These data suggest that MCAO-induced cortical infarction and neurological dysfunction is associated with neuronal depletion and vascular redistribution of brain NSE resulting in a measurable increase in plasma NSE. Such diffusion of NSE into the cerebral vasculature and systemic circulation from ischemic tissue can be expected to serve as a marker for the incidence of cerebral damage in acute and chronic ischemic brain infarcts.

Animals↗
PubMed1993

A Drosophila gene encoding a protein with similarity to diacylglycerol kinase is expressed in specific neurons.

A Drosophila gene encoding a protein with similarity to diacylglycerol kinase (DGK) was isolated by screening a genomic DNA library with a human DGK cDNA under low-stringency hybridization conditions. This putative Drosophila DGK gene (dDGK) maps to 43E on the right arm of chromosome 2. A dDGK cDNA with an open reading frame encoding a 517 amino acid protein was obtained in a screen of a 3-12-h embryonic cDNA library. In a 236-amino-acid overlap at their C-termini there is an identity of 52.5% between the dDGK protein and human DGK. The N-terminus of the Drosophila protein is not similar to human DGK, and contains clusters of polar amino acids. dDGK is transcribed in the embryonic, pupal and adult stages, with little expression during the larval stages. Transcripts of 1.7-2.2 kb, 3.5 kb, 3.7 kb and 6.6 kb are seen, although most of the smaller transcripts may be from genes with similarity to dDGK. In stage-16 and stage-17 embryos, dDGK transcripts are limited to the central nervous system and head. There is a particularly high level of expression in the cell bodies of the larval photoreceptor organ, and in the cell bodies of the ventral unpaired median neurons. The dDGK protein may be involved in regulating signal transduction in these specific neurons.

Amino Acid Sequence↗
PubMed2001

Encoding of categories by noncategory-specific neurons in the inferior temporal cortex.

In order to understand how the brain codes natural categories, e.g., trees and fish, recordings were made in the anterior part of the macaque inferior temporal (IT) cortex while the animal was performing a tree/nontree categorization task. Most single cells responded to exemplars of more than one category while other neurons responded only to a restricted set of exemplars of a given category. Since it is still not known which type of cells contribute and what is the nature of the code used for categorization in IT, we have performed an analysis on single-cell data. A Kohonen self-organizing map (SOM), which uses an unsupervised (competitive) learning algorithm, was used to study the single cell responses to tree and nontree images. Results from the Kohonen SOM indicated that the collected neuronal data consisting of spike counts was sufficient to account for a good level of categorization success (approximately 83%) when categorizing a group of 200 trees and nontrees. Contrary to intuition, the results of the investigation suggest that the population of category-specific neurons (neurons that respond only to trees or only to nontrees) was unimportant to the categorization. Instead, a large majority of the neurons that were most important to the categorization was found to belong to a class of more broadly tuned cells, namely, cells that responded to both categories but that favored one category over the other by seven or more images. A simple algebraic operation (without the Kohonen SOM) between the above-mentioned noncategory-specific neurons confirmed the contribution of these neurons to categorization. Thus, the modeling results suggest (1) that broadly tuned neurons are critical for categorization, and (2) that only one additional layer of processing is required to extract the categories from a population of IT neurons.

Animals↗
PubMed1982

Development of neuron-specific enolase immunoreactivity in avian nervous tissue in vivo and in vitro.

Neuron-specific enolase (NSE) is a glycolytic isoenzyme that is primarily located in neurons and neuroendocrine cells. The development of NSE immunoreactivity in th avian nervous system at the level of the hind limb has been examined using immunocytochemical methods. NSE immunoreactivity is first detected in ventral horn motor neurons and dorsal root ganglion neurons at embryonic day 9-10. This is at least 2-3 days after some neurons in both these populations are capable of electrical activity. The glycogen body, a non-neuronal structure, also exhibits NSE (+) staining, but the onset of this immunoreactivity is earlier, at 8 days of embryonic development. NSE immunoreactivity was absent from the cell bodies of paravertebral sympathetic ganglia throughout development, but was present in cellular processes and terminals in the adult ganglia. NSE immunoreactivity also develops in tissue cultures containing cells of neural tube and neural crest origin.

Animals↗
PubMed1987

Expression of cytokeratin and neuron-specific enolase in small cell carcinomas of the lung.

Using a polyclonal antibody against human epidermal keratins and a monoclonal antibody against cytokeratins characteristic of simple epithelia, and the Avidin-Biotin system of immunohistochemistry, we have demonstrated cytokeratin expression in 46% and in 60% of small cell carcinomas of the lung at autopsy respectively. The latter gave a diffuse stronger reaction product than the polyclonal antibody. The results suggest that there is a cytokeratin rich and a cytokeratin poor type of small cell carcinoma. Neuron-specific enolase immunohistochemistry was positive in 60% of the cases. Coexpression with cytokeratin was seen in ten cases (30%). The expression of cytokeratin and neuron-specific enolase in small cell carcinomas strongly suggests that they are of an epithelial origin, but are capable of neuroendocrine differentiation.

Aged↗
PubMedDate not supplied

Neuron-specific enolase in non-neoplastic lung diseases, a marker of hypoxemia?

Neuron-specific enolase (NSE) is a glycolytic enzyme localized within neuronal and neuroendocrine tissues. Serum NSE is widely used as a marker of neuroendocrine tumors. Moderate serum NSE elevation has been reported in some patients with benign lung diseases. We decided to investigate whether the elevation of serum NSE in non-neoplastic lung diseases is connected with hypoxemia and to what extent the recovery of sufficient ventilation with a respirator may influence NSE concentrations. Serum NSE was estimated by means of radioimmunoassay in 83 patients with various non-neoplastic lung diseases. Serum NSE exceeding 12.5 micrograms/L was significantly more frequent in patients with marked hypoxemia (PaO2 < 6.67 kPa; p = 0.03) than in others. The median NSE value in the group of patients without respiratory failure (Ro) was 7.2 micrograms/L (10% > 12.5 micrograms/L), in the group of patients with respiratory failure not requiring mechanical ventilation (Rf) it was 8.5 micrograms/L (24% > 12.5 micrograms/L), and in the group of patients with respiratory failure requiring mechanical ventilation (Rfv) 13.1 micrograms/L (60% > 12.5 micrograms/L). The differences between the Rfv group and the other two groups (Rf and Ro) were significant (P = 0.049 and p = 0.0004, respectively). During successful mechanical ventilation elevated serum NSE decreased to values below the cutoff in 8/10 patients. We conclude that serum NSE elevation is a frequent event in patients with terminal hypoxemia in the course of benign lung diseases. Normalization of serum NSE is observed in the majority of patients during the first week of mechanical ventilation.

Adult↗
PubMed1999

Neuron-restrictive silencer elements mediate neuron specificity of adenoviral gene expression.

Neuron-restrictive silencer elements (NRSEs) were used to target the gene expression of adenoviral vectors specifically to neuron cells in the central nervous system. By generating adenoviral constructs in which NRSE sequences were placed upstream from the ubiquitous phosphoglycerate kinase promoter, the specificity of expression of a luciferase reporter gene was tested in both cell lines and primary cultures. Whereas transgene expression was negligible in nonneuronal cells following infection with an adenovirus containing 12 NRSEs, neuronal cells strongly expressed luciferase when infected with the same adenovirus. The NRSEs restricted expression of the luciferase gene to neuronal cells in vivo when adenoviruses were injected both intramuscularly into mice and intracerebrally into rats. This NRSE strategy may avoid side effects resulting from the ectopic expression of therapeutic genes in the treatment of neurological diseases. In particular, it may allow the direct transfection of motor neurons without promoting transgene expression within inoculated muscles or the secretion of transgene products into the bloodstream.

Adenoviridae↗
PubMed2004

Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice.

Apolipoprotein E (apoE) is found in amyloid plaques and neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains, but its role in their pathogenesis is unclear. Previously, we found C-terminal-truncated fragments of apoE in AD brains and showed that such fragments can cause neurodegeneration and can induce NFT-like inclusions in cultured neuronal cells and in transgenic mice. Here, we analyzed apoE fragmentation in brain tissue homogenates from transgenic mice expressing apoE3 or apoE4 in neurons [neuron-specific enolase (NSE)-apoE] or astrocytes [glial fibrillary acidic protein (GFAP)-apoE] by Western blotting. The C-terminal-truncated fragments of apoE accumulated, in an age-dependent manner, in the brains of NSE-apoE4 and, to a significantly lesser extent, NSE-apoE3 mice; however, no fragments were detected in GFAP-apoE3 or GFAP-apoE4 mice. In NSE-apoE mice, the pattern of apoE fragmentation resembled that seen in AD brains, and the fragmentation was specific for certain brain regions, occurring in the neocortex and hippocampus, which are vulnerable to AD-related neurodegeneration, but not in the less vulnerable cerebellum. Excitotoxic challenge with kainic acid significantly increased apoE fragmentation in NSE-apoE4 but not NSE-apoE3 mice. Phosphorylated tau (p-tau) also accumulated in an age-dependent manner in NSE-apoE4 mice and, to a much lesser extent, in NSE-apoE3 mice but not in GFAP-apoE3 or GFAP-apoE4 mice. Intraneuronal p-tau inclusions in the hippocampus were prominent in 21-month-old NSE-apoE4 mice but barely detectable in NSE-apoE3 mice. Thus, the accumulation of potentially pathogenic C-terminal-truncated fragments of apoE depends on both the isoform and the cellular source of apoE. Neuron-specific proteolytic cleavage of apoE4 is associated with increased phosphorylation of tau and may play a key role in the development of AD-related neuronal deficits.

Aging↗
PubMed2004

Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells.

Alternative splicing provides a versatile mechanism of gene regulation, which is often subverted in disease. We have used customized oligonucleotide microarrays to interrogate simultaneously the levels of expression of splicing factors and the patterns of alternative splicing of genes involved in tumor progression. Analysis of RNAs isolated from cell lines derived from Hodgkin lymphoma tumors indicate that the relative abundance of alternatively spliced isoforms correlates with transformation and tumor grade. Changes in expression of regulators were also detected, and a subset sample was confirmed at the protein level. Ectopic expression of neuron-specific splicing regulatory proteins of the Nova family was observed in some cell lines and tumor samples, correlating with expression of a neuron-specific mRNA isoform of JNK2 kinase. This microarray design can help assess the role of alternative splicing in a variety of biological and medical problems and potentially serve as a diagnostic tool.

Alternative Splicing↗
PubMed1985

Developmental changes of neuron-specific enolase in human brain: an immunohistochemical study.

Developmental changes of neurons containing neuron-specific enolase (NSE) in human brain were studied in various areas of the central nervous system by immunohistochemistry with the peroxidase-antiperoxidase (PAP) method. In the brain stem, Purkinje cells, dentate nucleus, globus pallidus and thalamus, the number of NSE-positive neurons increased from an early period in gestation. However, in the pontine nucleus and putamen, it gradually increased along with decreasing cellularity later in gestation and in the infantile period. In the cerebral cortex, NSE-positive neurons developed as late as in the putamen and their cellularity increased earlier in the 5th layer than in the 3rd layer. Developmental changes of NSE-positive neurons parallel phylogenesis. The appearance of NSE-positive neurons can be a marker of neuronal maturation.

Adolescent↗
PubMed1999

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Adult↗
PubMed1998

Regulation of neuronal specification in the zebrafish spinal cord by Delta function.

The vertebrate spinal cord consists of a large number of different cell types in close proximity to one another. The identities of these cells appear to be specified largely by information acquired from their local environments. We report here that local cell-cell interactions, mediated by zebrafish homologues of the Drosophila melanogaster neurogenic gene, Delta, regulate specification of diverse neuronal types in the ventral spinal cord. We describe identification of a novel zebrafish Delta gene expressed specifically in the nervous system and show, by expressing a dominant negative form of Delta protein in embryos, that Delta proteins mediate lateral inhibition in the zebrafish spinal cord. Furthermore, we find that Delta function is important for specification of a variety of spinal cord neurons, suggesting that lateral inhibition serves to diversify neuronal fate during development of the vertebrate spinal cord.

Animals↗
PubMed1984

Immunohistochemical demonstration of neuron-specific enolase in neoplasms of the CNS and other tissues.

In normal conditions, neuron-specific enolase (NSE) is histochemically demonstrable only in neurons and cells of the amine precursor uptake and decarboxylation (APUD) system. This has been found not to be true for neoplastic cells. Several types of CNS tumors, including glioblastoma, astrocytoma, oligodendroglioma, ependymoma, medulloblastoma, pineocytoma , meningioma, and choroid plexus papilloma, focally stained positively for NSE. Reactive astrocytes were also frequently positive. In the peripheral nervous system, neuroblastoma, ganglioneuroma, and paraganglioma stained positively for NSE. A number of non-APUD tumors were focally positive. These included schwannoma, carcinoma and fibroadenoma of the breast, renal cell carcinoma, giant cell tumor of the tendon sheath, and chordoma. Caution should be exercised in relying on the immunohistochemical demonstration of NSE as a diagnostic marker in those tumors that do not belong to the APUD cell system. It seems of little value as evidence of differentiation in CNS tumors.

14-3-3 Proteins↗
PubMed1986

Neuron specific enolase expression in carcinoma of the lung.

The value of neuron specific enolase (NSE) immunoreactivity as a marker for small cell lung cancer (SLC) has been assessed using a monoclonal antibody (MCAB) against NSE, MCAB specificity was confirmed using purified enolase isoenzymes, sections of human brain, a panel of lung tumours, neuroendocrine and non-neuroendocrine tumours and normal tissues. Using this MCAB in radioimmunoassay and immunohistochemistry, NSE immunoreactivity was detected in all SCLC material examined. However, considerable reactivity was also observed in a number of non-small cell lung cancer cell lines and tumour biopsy specimens. Furthermore, intratumoral heterogeneity with respect to NSE immunostaining was observed in several cases. Factors which may underlie such intratumoral phenotypic diversity were assessed using flow cytometry together with MCABs directed against both NSE and non-neuronal enolase. Such studies revealed that enolase expression in cells which were no longer actively proliferating differed markedly from that of cells in exponential growth. Furthermore, cells grown under conditions of increasing hypoxia exhibited increased enolase expression relative to those grown under oxygenated conditions. It is concluded from these studies that NSE immunoreactivity per se is an unreliable marker for the SCLC phenotype.

Animals↗
PubMed2002

A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes.

BRAF35, a structural DNA-binding protein, initially was identified as a component of a large BRCA2-containing complex. Biochemical analysis revealed the presence of a smaller core-BRAF35 complex devoid of BRCA2. Here we report the isolation of a six-subunit core-BRAF35 complex with the capacity to deacetylate histones, termed the BRAF-histone deacetylase complex (BHC), from human cells. BHC contains polypeptides reminiscent of the chromatin-remodeling complexes SWI/SNF and NuRD (nucleosome remodeling and deacetylating). Similar to NuRD, BHC contains an Mi2-like subunit, BHC80, and a PHD zinc-finger subunit as well as histone deacetylases 1/2 and an MTA-like subunit, the transcriptional corepressor CoREST. We show that BHC mediates repression of neuron-specific genes through the cis-regulatory element known as the repressor element 1 or neural restrictive silencer (RE1/NRS). Chromatin-immunoprecipitation experiments demonstrate the recruitment of BHC by the neuronal repressor REST. Expression of BRAF35 containing a single point mutation in the HMG domain of the protein abrogated REST-mediated transcriptional repression. These results demonstrate a role for core-BRAF35-containing complex in the regulation of neuron-specific genes through modulation of the chromatin structure.

Cell Nucleus↗
PubMedDate not supplied

Patterns of staining for neurone specific enolase in benign and malignant melanocytic lesions of the skin.

Neurone specific enolase (NSE) is a useful marker for melanoma independent of the criterion of melanogenesis. A range of benign and malignant melanocytic skin lesions has been studied to assess the diagnostic potential of staining for NSE. The detailed features of the presence and distribution of NSE in 47 skin lesions are presented. These include 3 junctional, 7 compound, 15 intradermal and 8 SPitz naevi; 6 superficial type, 2 lentigo maligna and 6 nodular melanomata. A progressive increase of staining for NSE from benign to malignant is seen. Spitz naevi could easily be differentiated from melanoma. An advantage of this stain is the simultaneous demonstration of the innervation of these lesions. We conclude that NSE is a useful aid to the diagnosis and assessment of melanocytic skin tumours and may prove of value in clarifying the nature of these enigmatic lesions.

Humans↗
PubMed1996

Serum neuron specific enolase: can it be a tumour marker for renal cell carcinoma?

Neuron specific enolase (NSE) is an isoenzyme of the glycolytic enzyme enolase. It is not only a marker for all types of neurons but also for all neuroendocrine or paraneuronal cells and various malignant tumours, even of non-neuroendocrine types. We had studied serum NSE in 25 consecutive patients with renal cell carcinoma (RCC). The study included 10 stage I, 3 stage II, 3 stage III-B and 9 stage IV-B patients. Both pretreatment and posttreatment levels were evaluated. Regardless of stage, overall we observed elevated levels of NSE in 80% (20/25) at diagnosis. After the appropriate treatment, according to the stage, there had been a statistically significant (p < 0.05) decrease in the serum levels in all stage I, II and III-B patients. The posttreatment values were not available for stage IV-B patients because they did not come for follow-up. The preliminary results of our study revealed that serum NSE may be considered as a useful marker in the evaluation and surveillance of RCC.

Adult↗
PubMed1998

The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity.

Cyclin-dependent kinase 5 (Cdk5) and its neuron-specific regulator p35 are essential for neuronal migration and for the laminar configuration of the cerebral cortex. In addition, p35/Cdk5 kinase concentrates at the leading edges of axonal growth cones and regulates neurite outgrowth in cortical neurons in culture. The Rho family of small GTPases is implicated in a range of cellular functions, including cell migration and neurite outgrowth. Here we show that the p35/Cdk5 kinase co-localizes with Rac in neuronal growth cones. Furthermore, p35 associates directly with Rac in a GTP-dependent manner. Another Rac effector, Pak1 kinase, is also present in the Rac-p35/Cdk5 complexes and co-localizes with p35/Cdk5 and Rac at neuronal peripheries. The active p35/Cdk5 kinase causes Pak1 hyperphosphorylation in a Rac-dependent manner, which results in down-regulation of Pak1 kinase activity. Because the Rho family of GTPases and the Pak kinases are implicated in actin polymerization, the modification of Pak1, imposed by the p35/Cdk5 kinase, is likely to have an impact on the dynamics of the reorganization of the actin cytoskeleton in neurons, thus promoting neuronal migration and neurite outgrowth.

Animals↗