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PubMed1999

Increase of neuron-specific enolase in patients with Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative human disorder with an incidence of one case per 1000000 per year. Recently new diagnostic tests such as neuron-specific enolase (NSE), S-100, tau-protein and protein 14-3-3 have been established as markers in prion diseases. NSE is elevated in case of rapid nerve cell loss so quantitative measurement of NSE in cerebrospinal fluid (CSF) might correlate with the disease progression. To further evaluate this hypothesis we analysed longitudinal CSF samples from 16 CJD patients. The first spinal tap was taken two weeks after the first clinical signs of a neurodegenerative disorder. This showed an elevation of NSE which continued during the course of the disease. Longitudinal examination of neuron-specific enolase in cerebrospinal fluid therefore may be useful for differentiation between CJD and other dementias.

14-3-3 Proteins↗
PubMed1999

Neuron-specific and developmental regulation of the synapsin II gene expression in transgenic mice.

Synapsin II, a major phosphoprotein of synaptic vesicles, is believed to function in neurotransmitter release as well as in synapse formation. The expression of the synapsin II gene is neuron-specific, and correlates temporally with synaptogenesis. To understand the mechanisms by which the expression of the synapsin II gene is regulated in vivo, we generated transgenic mice carrying a 5.1-kb 5'-flanking sequence of the murine synapsin II gene fused to the firefly luciferase reporter gene. The synapsin II-luciferase transgene is specifically expressed in neural tissues, such as brain and spinal cord, but not in non-neural tissues. Throughout the brain, the expression of the transgene is widely distributed, and restricted only to neuronal cells. Moreover, the expression of the transgene is developmentally regulated, with a temporal profile similar to that of endogenous synapsin II expression. These results indicate that the 5.1-kb flanking sequence of the murine synapsin II gene contains cis-regulatory elements that are required for directing neuron-specific and synaptogenesis-regulated expression in vivo.

Age Factors↗
PubMed1994

Expression of neuron-specific enolase in the developing rat retina as revealed by immunocytochemistry.

Expression of neuron-specific enolase (NSE) in retinal neurons was immunocytochemically investigated during the development of the rat retina. At embryonic day 14 (E14), the first immunoreaction of NSE was identified in the pigment epithelium. NSE-positive ganglion cells occurred at the inner surface of the retina by E15. Horizontal cells and photoreceptor cells became stainable for NSE in the outer portion of the neuroblastic layer as early as E17. At E20, when the majority of ganglion cells were intensely positive for NSE, immunoreactive amacrine cells first appeared at the outer surface of the developing inner plexiform layer. It was not until postnatal day 7 (P7) that NSE-positive bipolar cells occurred in the middle of the inner nuclear layer. At this stage, most of the photoreceptor cells located in the outer nuclear layer were immunolabeled, whereas the ectopic photoreceptor cells in the inner nuclear layer were devoid of immunoreaction. Most identifiable retinal neurons became strongly immunostained for NSE by P14. Our results indicate that the NSE expression of retinal neurons occurs just after their migration to the final location and prior to establishing the synaptic structures. In this paper, the characteristic sequence in which different types of retinal neurons exhibit NSE immunoreaction is discussed in the light of certain autoradiographic data on the sequence of retinal cell genesis.

Aging↗
PubMed1991

Neuron-specific thresholds of aluminum toxicity in vitro. A comparative analysis of dissociated fetal rabbit hippocampal and motor neuron-enriched cultures.

Mature dissociated motor neuron-enriched and hippocampal neuron cultures derived from fetal New Zealand white rabbits were continuously exposed to 1, 10, 25, 50, or 100 microM AlCl3 in a chemically defined medium for 14 days. Motor neuron-enriched cultures exposed to low concentrations (1 or 10 microM) of AlCl3 remained viable for the entire experiment but developed perikaryal and neuritic inclusions composed of phosphorylated neurofilament. Similar inclusions developed in cultures exposed to 25 and 50 microM AlCl3, but motor neurons did not survive beyond 10 days exposure. The 100 microM AlCl3-supplemented medium induced cell death within 72 hours without development of inclusions. In contrast, hippocampal neurons exposed to 1, 10, or 25 microM AlCl3 developed no morphological changes or inclusions. Although hippocampal cultures exposed to 50 or 100 microM AlCl3 developed perinuclear and proximal neuritic inclusions of phosphorylated neurofilament after 10 days, they remained viable. These in vitro morphological observations demonstrate a 10-fold greater sensitivity of spinal motor neurons to aluminum toxicity when compared with hippocampal neurons and suggest that the earlier observations of neuron-specific thresholds of aluminum toxicity in vivo are related to unique regulatory mechanisms of neurofilament biosynthesis and catabolism within distinct neuronal cell populations.

Aluminum↗
PubMed1982

Regulatory peptides and neuron-specific enolase in the respiratory tract of man and other mammals.

This short review deals with the distribution and cellular localization, in the respiratory tract, of five regulatory peptides (substance P, bombesin, vasoactive intestinal polypeptide (VIP), cholecystokinin, and somatostatin) and of a newly discovered neuroendocrine enzyme marker, neuron-specific enolase. Bombesin is found in typical mucosal endocrine cells, whereas the other regulatory peptides--principally substance P and VIP--are found, in significant concentrations, in autonomic nerves of the wall of the airways. Substance P, a putative sensory neurotransmitter, is found in autonomic nerves closely associated with the mucosal epithelium and the bronchial smooth muscle. VIP nerves, on the other hand, appear predominantly to innervate blood vessels, seromucous glands of the upper respiratory tract, and bronchial smooth muscle. The presence of neuron-specific enolase in both mucosal APUD cells and autonomic nerves has established this newly discovered neuronal enzyme as a useful marker for the entire neuroendocrine system of the lung and its derivative neoplasms.

APUD Cells↗
PubMed1995

Cerebrospinal fluid neuron-specific enolase in Alzheimer's disease and vascular dementia.

Levels of neuron-specific enolase (NSE), a glycolytic enzyme localized in neurons, were measured in serum and cerebrospinal fluid (CSF) of patients with early-onset (e-AD) and late-onset (l-AD) Alzheimer's disease, vascular dementia (VD) and controls. Mean CSF NSE levels in patients with Alzheimer's disease did not significantly differ from those in controls, although in the AD group a correlation was found between NSE levels and severity of cognitive deficits. In VD patients, CSF NSE was lower than in controls or in AD patients. These findings are of physiopathological interest but suggest that CSF NSE is not a useful biological marker in dementia disorders.

Age of Onset↗
PubMed2001

Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment.

Mutations were identified in the Cu/Zn superoxide dismutase gene (SOD1) in approximately 15% of patients with familial amyotrophic lateral sclerosis. Transgenic animals expressing mutant SOD1 in all tissues develop an ALS-like phenotype. To determine whether neuron-specific expression of mutant SOD1 is sufficient to produce such a phenotype, we generated transgenic animals carrying the G37R mutation that is associated with the familial form of ALS (FALS), which is driven by the neurofilament light chain promoter. The transgenic animals express high levels of the human SOD1 protein in neuronal tissues, especially in the large motor neurons of the spinal cord, but they show no apparent motor deficit at up to 1.5 years of age. Our animal model suggests that neuron-specific expression of ALS-associated mutant human SOD1 may not be sufficient for the development of the disease in mice.

Amino Acid Substitution↗
PubMed1990

Chromogranin A, neuron-specific enolase and synaptophysin as neuroendocrine cell markers in the diagnosis of tumours of the gastro-entero-pancreatic system.

Neuroendocrine (NE) tumours of the gastro-entero-pancreatic tract were analysed immunohistochemically for the expression of chromogranin A, neuron-specific enolase and synaptophysin. In all cases at least one marker was present and in 17 out of 19 investigated neoplasms, at least one of the three markers could be demonstrated in more than 75% of the NE tumour cells. Monoclonal antibody chromogranin A stained a much higher proportion of NE cells in tumours with hormonal activity than in hormonally inactive ones. Immunostaining of the primary tumour as compared to its respective metastases was almost identical. Thus, chromogranin A, neuron-specific enolase and synaptophysin identify NE tumours and their metastases regardless of their localization and their state of hormonal activity. As 'panendocrine' markers of NE tumours they are of special diagnostic value in NE tumours that do not produce hormones and peptides.

Adult↗
PubMed1997

[An antibody recognizing neuron specific tubulin].

A 20-residue peptide corresponding to the C-terminal amino acid sequence of rat nestin was synthesized by the solid phase method. The anti-peptide antibody (designated Anti-Nes-2) against nestin was prepared. Western blots showed that Anti-Nes-2 recognized not only mouse nestin with a MW of 240 kD but also a band with a MW of 50 kD. N-terminal amino acid sequence showed that this 50 kD protein is alpha-tubulin. Western blots with Anti-Nes-2 and with monoclonal antibodies against alpha- and beta-tubulin revealed that this 50 kD band could only be detected in different stages of mouse brain and in the primary culture of neural precursor cells (NPCs), with higher expression during the development of mouse brain and the maturation of NPCs; whereas alpha- and beta-tubulin were expressed in different cell lines and tissues of adult mouse. Taken together, these results indicate that 50 kD protein recognized by Anti-Nes-2 is a neuron-specific alpha-tubulin and could be a neuron-specific posttranslational modification isotype of alpha-tubulin.

Animals↗
PubMed1995

Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent.

To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using a 1 kb hamster cDNA clone containing the 0.76 kb HPrP open reading frame under control of the neuron-specific enolase promoter. In these mice, expression of HPrP was detected only in brain tissue, with highest levels found in neurons of the cerebellum, hippocampus, thalamus, and cerebral cortex. These transgenic mice were susceptible to infection by the 263K strain of hamster scrapie with an average incubation period of 93 days, compared to 72 days in normal hamsters. In contrast, nontransgenic mice were not susceptible to this agent. These results indicate that neuron-specific expression of the 1 kb HPrP minigene including the HPrP open-reading frame is sufficient to mediate susceptibility to hamster scrapie, and that HPrP expression in nonneuronal brain cells is not necessary to overcome the TSE species barrier.

Animals↗
PubMed2006

Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation.

BACKGROUND: Accurate prediction of survival to hospital discharge in patients who achieve return of spontaneous circulation after cardiopulmonary resuscitation (CPR) has significant ethical and socioeconomic implications. We investigated the prognostic performance of serum neuron-specific enolase (NSE), a biochemical marker of ischemic brain injury, after successful CPR. METHODS: In-hospital or out-of-hospital patients with nontraumatic normothermic cardiac arrest who achieved return of spontaneous circulation (ROSC) following at least 5 minutes of CPR were eligible. Neuron-specific enolase levels were assessed immediately, 6 hours, 12 hours and 2 days after ROSC. Subjects were followed to death or hospital discharge. RESULTS: Seventeen patients (7 men, 10 women) were enrolled during a 1-year period. Median (range) NSE levels in survivors and non-survivors respectively were as follows: immediately after ROSC: 14.0 microg/L (9.1-51.4 microg/L) versus 25.9 microg/L (10.2-57.5 microg/L); 6 hours after ROSC: 15.2 microg/L (9.7-30.8 microg/L) versus 25.6 microg/L (12.7-38.2 microg/L); 12 hours after ROSC: 14.0 microg/L (8.6-32.4 microg/L) versus 28.5 microg/L (11.0-50.7 microg/L); and 48 hours after ROSC: 13.1 microg/L (7.8-29.5 microg/L) versus 52.0 microg/L (29.1-254.0 microg/L). Non-survivors had significantly higher NSE levels 48 hours after ROSC than surivors (p = 0.04) and showed a trend toward higher values during the entire time course following ROSC. An NSE concentration of >30 microg/L 48 hours after ROSC predicted death with a high specificity (100%: 95% confidence interval [CI] 85%-100%), and a level of 29 microg/L or less at 48 hours predicted survival with a high specificity (100%: 95% CI 83%-100%). CONCLUSIONS: Serum NSE levels may have clinical utility for the prediction of survival to hospital discharge in patients after ROSC following CPR over 5 minutes in duration. This study is small, and our results are limited by wide confidence intervals. Further research on ability of NSE to facilitate prediction and clinical decision-making after cardiac arrest is warranted.

Adult↗
PubMed1992

Demonstration of specific neuronal cell groups in rat brain by beta-galactosidase enzyme histochemistry.

beta-Galactosidase activity as illuminated by the indigogenic X-gal staining method has been used to demonstrate the presence of genetically modified cells carrying the reporter gene lacZ, coding for the E. coli enzyme. Endogenous activity has been assumed to be minimal since the pH optimum for the mammalian enzyme is 3.5-5.5, while the pH optimum for the E. coli enzyme (and thus of the staining procedure usually employed) is 7.3. Background staining has been reported to be limited to pericytes and a few specific neuronal cell groups. In contrast, our investigations of normal rat brain anatomy demonstrate that many specific neuronal cell groups possess endogenous beta-galactosidase activity when staining is performed at physiological pH. This suggests that background staining of endogenous beta-galactosidase activity in the rat brain has been underestimated. In addition, such specific activity would afford an additional means of identification and illustration of these cells.

Animals↗
PubMed1995

Characterization of nervana, a Drosophila melanogaster neuron-specific glycoprotein antigen recognized by anti-horseradish peroxidase antibodies.

Antibodies to the plant glycoprotein horseradish peroxidase (HRP) are used extensively to identify neurons in Drosophila and other insects. We are interested in characterizing the gene product(s) recognized by anti-HRP antibodies because it may be important for nervous system function and/or development. Here we identify and purify from adult Drosophila heads an anti-HRP-reactive Mr 42K glycoprotein that is likely to be the major contributor to neuronal specific anti-HRP staining. Several different monoclonal antibodies to the purified 42K glycoprotein recognize up to three proteins with distinct mobilities between Mr 38K and 42K that vary as a function of developmental age. We have collectively named these components Nervana (nerve antigen), because the monoclonal antibodies also specifically stain cultured neurons and embryonic nervous system with a pattern indistinguishable from anti-HRP staining. Western blots indicate the presence of immunologically similar proteins in a wide variety of insect species and in nac (neurally altered carbohydrate) mutant Drosophila flies that lack anti-HRP staining in adult nervous system. It should now be possible to undertake a full biochemical and functional characterization of Nervana in Drosophila.

Aging↗
PubMed1997

Purification, characterization, and in vitro phosphorylation of the neuron-specific membrane-associated protein SCG10.

SCG10 is a neuron-specific, developmentally regulated protein which is highly enriched in growth cones. Sequence homology indicates that it is related to the phosphoprotein stathmin or Op18, an in vitro and in vivo substrate for several serine/threonine kinases which are involved in a variety of signaling pathways. As a first step to examine the biochemical properties of SCG10, the protein was expressed in Escherichia coli and purified to apparent homogeneity. The purified protein was used in in vitro phosphorylation assays. SCG10 was phosphorylated by MAP kinase, cAMP-dependent protein kinase, cGMP-dependent protein kinase, p34cdc2 kinase, DNA-dependent protein kinase, Ca2+/calmodulin kinase II, and casein kinase II. The protein was not a substrate for casein kinase I and protein kinase C. SCG10 was phosphorylated by src tyrosine kinase, which demonstrates that the protein can be phosphorylated in vitro on a tyrosine residue. Our data suggest that SCG10 is a phosphoprotein which might be involved in signal transduction in neurons.

Amino Acid Sequence↗
PubMed2006

Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain.

SMCT1 is a sodium-coupled (Na(+)-coupled) transporter for l-lactate and short-chain fatty acids. Here, we show that the ketone bodies, beta-d-hydroxybutyrate and acetoacetate, and the branched-chain ketoacid, alpha-ketoisocaproate, are also substrates for the transporter. The transport of these compounds via human SMCT1 is Na(+)-coupled and electrogenic. The Michaelis constant is 1.4 +/- 0.1 mm for beta-d-hydroxybutyrate, 0.21 +/- 0.04 mm for acetoacetate and 0.21 +/- 0.03 mm for alpha-ketoisocaproate. The Na(+) : substrate stoichiometry is 2 : 1. As l-lactate and ketone bodies constitute primary energy substrates for neurons, we investigated the expression pattern of this transporter in the brain. In situ hybridization studies demonstrate widespread expression of SMCT1 mRNA in mouse brain. Immunofluorescence analysis shows that SMCT1 protein is expressed exclusively in neurons. SMCT1 protein co-localizes with MCT2, a neuron-specific Na(+)-independent monocarboxylate transporter. In contrast, there was no overlap of signals for SMCT1 and MCT1, the latter being expressed only in non-neuronal cells. We also demonstrate the neuron-specific expression of SMCT1 in mixed cultures of rat cortical neurons and astrocytes. This represents the first report of an Na(+)-coupled transport system for a major group of energy substrates in neurons. These findings suggest that SMCT1 may play a critical role in the entry of l-lactate and ketone bodies into neurons by a process driven by an electrochemical Na(+) gradient and hence, contribute to the maintenance of the energy status and function of neurons.

Animals↗
PubMedDate not supplied

[Psychomotor development of newborn infants at risk with reference to the neuron-specific enolase].

In a prospective study the psychomotor development of an unselected collective of risk newborn infants up to the end of the second year of life was examined. 199 children have developed normal, 21 showed developmental abnormalities, 84 light to moderate disturbances, and 30 severe disabilities. Already in the newborn period the concentration of neuron-specific enolase in the serum was evaluated. The NSE could be an indicator of brain damage. The determined values of NSE showed a log-normal-distribution at the three times (cord-blood, first or second day of life, third or fourth day of life, and ninth to eleventh day of life). Significant relationship between the psychomotor development during the first two years of life and of NSE-concentration was not found. Nevertheless the diagnostic value of the NSE is better with a specificity of 47.7% and a sensitivity of 80.0% than those of the results of intracranial ultrasound examination or of the erythrocytic-density-test. In contrast to these results the use of the neuron-specific enolase alone for the prediction of individual prognosis of children is not be recommended.

Brain Damage, Chronic↗
PubMed1996

Modification of human neuron-specific enolase for application to radioimmunoassay.

A recombinant human neuron-specific enolase (R-NSE), isolated from Escherichia coli, could not be used in an RIA system because of instability upon labeling. To apply R-NSE to RIA and to simplify the purification procedure, the N- and C-terminals of R-NSE were modified by tyrosine- and histidine-tagging, respectively. SY-NSE, containing one additional tyrosine residue, was obtained from both soluble and insoluble fractions. More derivatives tagged by two or four tyrosine residues were expressed, but only in the insoluble fraction. SY-NSE and SY-NSE.H6 (containing six histidine residues at C-terminal of SY-NSE) purified from the soluble fraction were applicable to the RIA system, indicating that the addition of a tyrosine residue at the terminal is effective if the antigen is unstable during labeling.

Base Sequence↗
PubMed2003

Neuron-specific enolase, nucleotides, nucleosides, purine bases, oxypurines and uric acid concentrations in cerebrospinal fluid of children with meningitis.

To determine the effects of meningitis on cerebral energy metabolism, cerebrospinal fluid concentrations of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high-performance liquid chromatography, and neuron-specific enolase by an enzyme immunoassay method, in 100 children with meningitis (45 bacterial, 46 viral and nine tuberculous), aged between 1 month and 13 years, and in 160 age-matched controls. Compared with controls, patients with bacterial meningitis showed high concentrations of hypoxanthine, xanthine and urate; patients with viral meningitis showed high concentrations of inosine, guanosine, xanthine, urate and neuron-specific enolase; and patients with tuberculous meningitis showed very high concentrations of inosine, xanthine and urate. Xanthine and urate concentrations were significantly higher in patients with tuberculous meningitis than in patients with viral or bacterial meningitis. These results suggest that in the acute stage of bacterial, viral and tuberculous meningitis, neuronal energy metabolism may be altered. The measurement of cerebrospinal xanthine and uric acid concentrations may be useful for the early diagnosis of a tuberculous origin.

Child↗