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Z Molnár

Publications and source records attributed to Z Molnár.

At least 19 recordsLinked to original sources
PubMed2005

Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate neocortices.

Laminar organization is a fundamental cytoarchitecture in mammalian CNS and a striking feature of the neocortex. ER81, a transcription factor, has recently been utilized as a marker of cells in the layer 5 of the neocortex. We further pursued the distribution of ER81 to investigate the identity of the ER81-expressing cells in the brain. Er81 transcript was expressed in a subset of pyramidal cells that were scattered throughout the entire width of layer 5. In the rat cortex, Er81 transcripts were first detected in the ventricular zone at E15, remained expressed in putative prospective layer 5 neurons during infant and juvenile stages. The ER81-expressing subpopulation in adult layer 5 neurons did not segregate with the phenotypes of the projection targets. By retrograde labeling combined with immunohistochemistry or reverse transcription-polymerase chain reaction analysis, we found ER81 expression in nearly all of the layer 5 neurons projecting to the spinal cord or to the superior colliculus, while in only one-third of the layer 5 neurons projecting to the contralateral cortex. Er81 was also detected in layer 5 neurons in a P2 Japanese macaque monkey but not in adult monkey cortices. These findings suggest that a neuron class defined by a molecular criterion does not necessarily segregate with that defined by an anatomical criterion, that ER81 is involved in cell differentiation of a subset of layer 5 projection neurons and that this mechanism is conserved among rodents and primates.

Aging↗
PubMed2005

Pentapeptides derived from Abeta 1-42 protect neurons from the modulatory effect of Abeta fibrils--an in vitro and in vivo electrophysiological study.

Short fragments and fragment analogues of beta-amyloid 1-42 peptide (Abeta1-42) display a protective effect against Abeta-mediated neurotoxicity. After consideration of our earlier results with in vitro bioassay of synthetic Abeta-recognition peptides and toxic fibrillar amyloids, five pentapeptides were selected as putative neuroprotective agents: Phe-Arg-His-Asp-Ser amide (Abeta4-8) and Gly-Arg-His-Asp-Ser amide (an analogue of Abeta4-8), Leu-Pro-Tyr-Phe-Asp amide (an analogue of Abeta17-21), Arg-Ile-Ile-Gly-Leu amide (an analogue of Abeta30-34), and Arg-Val-Val-Ile-Ala amide (an analogue of Abeta38-42). In vitro electrophysiological experiments on rat brain slices demonstrated that four of these peptides counteracted with the field excitatory postsynaptic potential-attenuating effect of Abeta1-42; only Arg-Val-Val-Ile-Ala amide proved inactive. In in vivo experiments using extracellular single-unit recordings combined with iontophoresis, all these pentapeptides except Arg-Val-Val-Ile-Ala amide protected neurons from the NMDA response-enhancing effect of Abeta1-42 in the hippocampal CA1 region. These results suggest that Abeta recognition sequences may serve as leads for the design of novel neuroprotective compounds.

Action Potentials↗
PubMed2004

Physiological and morphological changes in autolyzing Aspergillus nidulans cultures.

Physiological and morphological changes in carbon-limited autolyzing cultures of Aspergillus nidulans were described. The carbon starvation arrested conidiation while the formation of filamentous and "yeast-like" hyphal fragments with profoundly altered metabolism enabled the fungus to survive the nutritional stress. The morphological and physiological stress responses, which maintained the cellular integrity of surviving hyphal fragments at the expense of autolyzing cells, were highly concerted and regulated. Moreover, sublethal concentrations of the protein synthesis inhibitor cycloheximide or the mitochondrial uncoupler 2,4-dinitrophenol completely blocked the autolysis. In accordance with the propositions of the free-radical theory of ageing reactive oxygen species accumulated in the surviving fragments with a concomitant increase in the specific superoxide dismutase activity and a continuous decrease in cell viability. Glutathione was degraded extensively in carbon-starving cells due to the action of gamma-glutamyltranspeptidase, which resulted in a glutathione-glutathione disulfide redox imbalance during autolysis.

Aspergillus nidulans↗
PubMed2004

Increased glomerular permeability and pulmonary dysfunction following major surgery: correlation of microalbuminuria and PaO/FiO ratio.

BACKGROUND: The aim of our trial was to evaluate the ability of microalbuminuria as an indicator of outcome and to investigate its relationship with the postoperative respiratory dysfunction in the initial postoperative period in a high-risk patient group. METHODS: In our prospective, observational study patients were consecutively recruited following elective oesophagectomy, total gastrectomy, Whipple-resection of the pancreas and liver resection due to tumour removal. Microalbuminuria (expressed as urine albumin:creatinine ratio, M:Cr) was measured before (tp), and after surgery (t0, t6, t24, t48, t72). Multiple Organ Dysfunction Scores were monitored on ICU admission than daily (t1, t2, t3). For statistical analysis, Wilcoxon's rank-sum test, Mann-Whitney's U-test, receiver operating characteristic curve analysis and Spearman's rho test were used as appropriate. RESULTS: One hundred and forty patients (118 survivors and 22 non-survivors) were recruited. Significantly higher Multiple Organ Dysfunction Scores were observed in non-survivors throughout the study period (P < 0.001). Microalbuminuria (Cr) increased significantly (P < 0.01) on admission to the ICU (t0) compared with the preoperative levels, but levels returned to normal within 6 h and remained so for the rest of the study. There was a significant difference between survivors and non-survivors at t0 (P < 0.01). However the ROC curve indicated that M:Cr is not a reliable descriptor of outcome. Comparison of Cr values with the PaO2/FiO2 ratio showed an inverse relationship on admission, which remained so for t24 and t48. CONCLUSION: M:Cr measured on admission to the ICU was significantly higher in non-survivors than in survivors, and also showed an inverse relationship with the PaO2/FiO2 ratio following extended abdominal surgery. However, on admission, M:Cr did not discriminate survivors from non-survivors. Further studies are required to evaluate the prognostic value of this test for postoperative patients with risk of respiratory failure.

Aged↗
PubMed2003

Continuous epidural or intercostal analgesia following thoracotomy: a prospective randomized double-blind clinical trial.

BACKGROUND: Pain following thoracotomy is frequently associated with clinically important abnormalities of pulmonary function. The aim of the current study was to compare the efficacy of continuous thoracic epidural analgesia (EDA) to continuous intercostal (IC) block for postoperative pain and pulmonary function in a prospective, randomized, double-blinded clinical trial. METHODS: Fifty patients undergoing lung lobectomy for malignancies were randomized into two groups (25/group). Respiratory function (forced vital capacity, forced expiratory volume per 1 s/forced vital capacity, maximum midexpiratory flow rate, peak expiratory flow rate) were evaluated preoperatively, within 4 h after the operation and on the first postoperative day. Visual analog scale (VAS: 0-10) scores were evaluated four-hourly for 20 h. RESULTS: The VAS scores were significantly lower in the EDA versus IC group at the 4th, 8th, and 12th h of observation (mean +/- SD) 5.5 +/- 2.9 vs. 7.3 +/- 2.2 P = 0.04; 4.1 +/- 2.1 vs. 5.1 +/- 2.9 P = 0.02; 3.6 +/- 1.9 vs. 5.2 +/- 2.4 P = 0.01, respectively. Respiratory function parameters deteriorated significantly in both groups (P < 0.001) with no significant difference between the groups. Only one major adverse effect was detected: one patient suffered from rib osteomyelitis after intercostal cannulation and healed following surgical repair. CONCLUSIONS: The results of the present study show that following thoracotomy in the early postoperative period continuous EDA is a better pain relieving method than continuous IC block, as indicated by the VAS scores.

Adult↗
PubMed2002

Prenatal development of neural excitation in rat thalamocortical projections studied by optical recording.

To elucidate the formation of early thalamocortical synapses we recorded optical images with voltage-sensitive dyes from the cerebral cortex of prenatal rats by selective thalamic stimulation of thalamocortical slice preparations. At embryonic day (E) 17, thalamic stimulation elicited excitation that rapidly propagated through the internal capsule to the cortex. These responses lasted less than 15 ms, and were not affected by the application of glutamate receptor antagonists, suggesting that they might reflect presynaptic fiber responses. At E18, long-lasting (more than 300 ms) responses appeared in the internal capsule and in subplate. By E19, long-lasting responses increased in the cortical subplate. By E21, shortly before birth, the deep cortical layers were also activated in addition to the subplate. These long-lasting responses seen in the internal capsule and subplate were blocked by the antagonist perfusion, but the first spike-like responses still remained. The laminar location of the responses was confirmed in the same slices by Nissl staining and subplate cells were labeled by birthdating with bromodeoxyuridine at E13. Our results demonstrate that there is a few days delay between the arrival of thalamocortical axons at the subplate at E16 and the appearance of functional thalamocortical synaptic transmission at E19. Since thalamocortical connections are already functional within the subplate and in the deep cortical plate at embryonic ages, prenatal thalamocortical synaptic connections could influence cortical circuit formation before birth.

Action Potentials↗
PubMed2001

Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic neurons.

Perturbation of the homeostasis between proteases and their inhibitors has been associated with lesion-induced or degenerative neuronal changes. Protease nexin-1 (PN-1), a secreted serine protease inhibitor, is constitutively expressed in distinct neuronal cell populations of the adult CNS. In an earlier study we showed that transgenic mice with ectopic or increased expression of PN-1 in postnatal neurons have altered synaptic transmission. Here these mice are used to examine the impact of an extracellular proteolytic imbalance on long-term neuronal function. These mice develop disturbances in motor behavior from 12 weeks on, with some of the histopathological changes described in early stages of human motor neuron disease, and neurogenic muscle atrophy in old age. In addition, sensorimotor integration, measured by epicranial multichannel recording of sensory evoked potentials, is impaired. Our results suggest that axonal dysfunction rather than cell death underlies these phenotypes. In particular, long projecting neurons, namely cortical layer V pyramidal and spinal motor neurons, show an age-dependent vulnerability to PN-1 overexpression. These mice can serve to study early stages of in vivo neuronal dysfunction not yet associated with cell loss.

Amyloid beta-Protein Precursor↗
PubMed2001

A pH-sensitive chloride current in the chemoreceptor cell of rat carotid body.

1. Cardiorespiratory response to acidosis is initiated by the carotid body. 2. The direct effect of extracellular pH (pH(o)) on the chloride currents of isolated chemoreceptor cells of the rat carotid body was investigated using the whole-cell patch-clamp technique. 3. On applying intra- and extracellular solutions with a symmetrical high-Cl(-) content and with the monovalent cations replaced with membrane-impermeant ones, an inwardly rectifying Cl(-) current was found. 4. The current activated slowly and did not display any time-dependent inactivation. Current activation was present at membrane potentials negative to 0 mV (pH(o) = 7.0). 5. The current was activated by extracellular acidosis and inhibited by alkalosis in the physiologically relevant pH range of 7.0-7.8. 6. The current was reduced by 0.1 mM Cd2+ to the level of the leak current and by 1 mM anthracene-9-carboxylic acid (9-AC) to about 40 %, while 0.1 mM Ba2+ had no effect. 7. Application of 1 mM 9-AC caused a slow but statistically significant increase in the resting pH(i) (from a mean of 7.29 to 7.37 in 5 min) in clusters of chemoreceptor cells in CO(2)/HCO3(-)-buffered media as measured with carboxy-SNARF-1. 8. When membrane potential changes were estimated in the cell-attached mode, 1 mM 9-AC hyperpolarized three out of five tested cells (by 14 mV in average) incubated in CO(2)/HCO3(-)-buffered media. 9. In summary, chemoreceptor cells express an inwardly rectifying Cl(-) current, which is directly regulated by pH(o). The current may participate in intracellular acidification and membrane depolarization during acidic challenge.

Animals↗
PubMed2000

[Inflammatory markers after surgical treatment of esophageal tumors].

Oesophagectomies carry the risk of postoperative sepsis and mortality. The aim of this study was to evaluate the course of microalbuminuria, serum procalcitonin and C-reactive protein levels following oesophagectomies. Twenty one patients undergoing elective oesophagectomy were studied. Serum procalcitonin and C-reactive protein levels were determined on arrival on the intensive care unit (t0) and then daily (t24, t48, t72). Microalbuminuria (expressed as urine albumin:creatinine ratio, mg/mmol) was measured before (tpre), and after surgery (t0, t6, t24, t48, t72). For statistical analysis Wilcoxon test was used. The clinical course of the patients studied was uneventful during the first 72 hours as monitored by daily Multiple Organ Dysfunction Scores. Preoperative microalbuminuria levels were normal (< 10 mg/mmol). Levels at t0 increased significantly but then (t6-24) they returned to normal. Serum procalcitonin (normal: < 0.5 ng/ml) at t0 was slightly elevated and by t24 it increased significantly (median: 2.7 ng/ml, p < 0.05) and remained high for the rest of the study: t48-72. C-reactive protein was normal at t0 (< 10 mg/l) and by t24 it increased dramatically (up to 10-20 times to the normal value) until t48. At t72 it decreased, but still remained in the abnormal range. This study found, that the surgical insult resulted a significant increase in microalbuminuria, serum procalcitonin and C-reactive protein levels. However, the changes were not accompanied by the clinical signs of sepsis or multiple organ dysfunction in the early postoperative period following oesophagectomies.

Aged↗
PubMed2000

Conserved developmental algorithms during thalamocortical circuit formation in mammals and reptiles.

The general patterns of early thalamocortical development follow a similar sequence in all mammals. Thalamocortical projections descend through the ventral thalamus, advance in the internal capsule amongst cells which already possess dorsal thalamic projections, then reach the cerebral cortex by associating with subplate cells and their early corticofugal projections. Initially, the thalamic projections pause in the internal capsule and subplate layer. The interactions of the thalamocortical projections with the early generated, largely transient cells of the subplate, marginal zone, internal capsule and ventral thalamus are believed to play a crucial role in the organized deployment of thalamic projections and establishing a functional cortical architecture. Selective fasciculation, contact guidance and release of neurotrophic factors are thought to play roles in the development of thalamocortical projections. These ideas are obtaining support from recent work on reeler and other strains of mice. The evolutionary origin of these largely transient cells and the overlying logic of early developmental steps are not understood. The behaviour of the thalamocortical and corticothalamic projections at the corticostriatal junction is particularly puzzling. The comparison of early forebrain development in mammals and reptiles is beginning to reveal highly conserved cellular and molecular interactions during early thalamocortical development and to reveal homologies between telencephalic subdivisions.

Algorithms↗
PubMed2000

Disturbances of magnesium concentrations in various brain areas in Alzheimer's disease.

Our first project aimed at the determination of the average values of Mg in normal human brain (20 individuals, mean age 70 years). Ten brain parts were selected from both hemispheres. Determinations were carried out by inductively coupled plasma atomic emission spectrometry, inductively coupled plasma mass spectrometry and instrumental neutron activation analysis methods. In order to investigate the precision and the accuracy of the methods five biological standard reference materials were analyzed. The present results show a non-homogeneous distribution of Mg in normal human brain. Regions corresponding to each other in both hemispheres show almost identical concentration. The second goal was to study the possible Mg concentration changes in Alzheimer's disease (nine patients, ten brain parts). Mg values are found to be significantly decreased in brain regions of diseased patients compared to the controls.

Aged↗
PubMed2000

Development and evolution of thalamocortical interactions.

Thalamocortical projections in mammals must travel through a considerable portion of the newly formed subdivisions of the embryonic forebrain. They descend through the ventral thalamus, advance in the internal capsule amongst cells which already possess dorsal thalamic projections, traverse the striatocortical junction, and then reach the cerebral cortex by associating with subplate cells and their early corticofugal fibers. The interactions of the thalamocortical projections with early generated, largely transient cells of these regions are believed to play a crucial role in their deployment. These ideas are supported by recent work on reeler and other strains of mutant mice. While we are beginning to understand the basic pattern of the cellular and molecular interactions employed in mammalian thalamocortical development, comparative developmental studies hold the promise to reveal the underlying logic of these steps and the evolutionary origin of the mammalian cerebral cortex.

Animals↗
PubMed1999

Formation of cortical fields on a reduced cortical sheet.

Theories of both cortical field development and cortical evolution propose that thalamocortical projections play a critical role in the differentiation of cortical fields (; ). In the present study, we examined how changing the size of the immature neocortex before the establishment of thalamocortical connections affects the subsequent development and organization of the adult neocortex. This alteration in cortex is consistent with one of the most profound changes made to the mammalian neocortex throughout evolution: cortical size. Removing the caudal one-third to three-fourths of the cortical neuroepithelial sheet unilaterally at an early stage of development in marsupials resulted in normal spatial relationships between visual, somatosensory, and auditory cortical fields on the remaining cortical sheet. Injections of neuroanatomical tracers into the reduced cortex revealed in an altered distribution of thalamocortical axons; this alteration allowed the maintenance of their original anteroposterior distribution. These results demonstrate the capacity of the cortical neuroepithelium to accommodate different cortical fields at early stages of development, although the anteroposterior and mediolateral relationships between cortical fields appear to be invariant. The shifting of afferents and efferents with cortical reduction or expansion at very early stages of development may have occurred naturally in different lineages over time and may be sufficient to explain much of the phenotypic variation in cortical field number and organization in different mammals.

Aging↗
PubMed1999

Connections between cells of the internal capsule, thalamus, and cerebral cortex in embryonic rat.

The aim of our study is to understand the development of the earliest connections in the mammalian pallium by documenting the distribution of cells and fibres labelled from the dorsal and ventral thalamus, internal capsule, perirhinal, and dorsal cortex during the period between embryonic day (E) 14 and 17 by using carbocyanine dye tracing in fixed embryonic rat brains. Dye placed in the thalamus of E14 brains backlabels cells in the thalamic reticular nucleus and within the primitive internal capsule. Both anterograde and retrograde tracing confirmed that the first corticofugal projections reach the internal capsule by E14. At E15-E16, after the first cortical plate cells have migrated into the lateral cortex, some cells of the cortical plate and subplate and marginal zone, are backlabelled from the internal capsule, but still not from the dorsal thalamus, even with very long incubation periods. Crystal placement into the perirhinal cortex at E14-E15 labels numerous cells within the internal capsule, whereas no such cells are revealed from dorsal cerebral cortex until E17, suggesting that internal capsule cells establish early connections with the perirhinal and ventral but not dorsal cortex. We propose that the growth of axons from cortex to dorsal thalamus is delayed in two regions: first from E14-E15 at the lateral entrance of the internal capsule and then, from E16, closer to the thalamus, probably within the thalamic reticular nucleus. Subplate projections reach the proximity of the diencephalon at an early stage, but they might never enter the dorsal thalamus.

Animals↗
PubMed1999

Embryonic development of connections in turtle pallium.

We are interested in similarities and conserved mechanisms in early development of the reptilian and mammalian thalamocortical connections. We set out to analyse connectivity in embryonic turtle brains (Pseudemys scripta elegans, between stages 17 and 25), by using carbocyanine dye tracing. From the earliest stages studied, labelling from dorsal and ventral thalamus revealed backlabelled cells among developing thalamic fibres within the lateral forebrain bundle and striatum, which had similar morphology to backlabelled internal capsule cells in embryonic rat (Molnár and Cordery, 1999). However, thalamic crystal placements did not label cells in the dorsal ventricular ridge (DVR) at any stage examined. Crystal placements into both dorsal and lateral cortex labelled cells in the DVR and, reciprocally, DVR crystal placements labelled cells in the dorsal and lateral cortices. Retrograde labelling revealed that thalamic fibres arrive in the DVR and dorsal cortex by stage 19. The DVR received projections from the nucleus rotundus and the dorsal cortex exclusively from the perirotundal complex (including lateral geniculate nucleus). Thalamic fibres show this remarkable degree of specificity from the earliest stage we could examine with selective retrograde labelling (stage 19). Our study demonstrates that axons of similar cells are among the first to reach dorsal and ventral thalamus in mammals and reptiles. Our connectional analysis in turtle suggests that some cells of the mammalian primitive internal capsule are homologous to a cell group within the reptilian lateral forebrain bundle and striatum and that diverse vertebrate brains might use a highly conserved pattern of early thalamocortical development.

Animals↗
PubMed1999

Development of signals influencing the growth and termination of thalamocortical axons in organotypic culture.

Explants of embryonic or postnatal rat cortex, organotypically cultured in serum-free medium, maintain their structural integrity and their upper layers continue to mature. Coculture of portions of embryonic thalamus with cortical slices taken at different ages reveals a temporal cascade of cortical signals. (1) Slices of occipital cortex taken at E19 or earlier stimulate axonal outgrowth from explants of embryonic lateral geniculate nucleus but do not allow the fibers to invade. (2) In cortical slices taken after E19 but before P2, thalamic axons enter the slice, from any direction, and extend radially across the entire depth of the cortical plate without branching or terminating. (3) In slices taken after P2, fibers slow down, arborize, and terminate in the maturing layer 4 of the cortex. If the thalamic explant is placed against the pial surface of the cortical slice, axons still enter and branch in the same layer. These findings imply that the developing cortex expresses a diffusible growth-promoting factor and then itself becomes growth permissive, and finally the maturing layer 4 expresses a "stop signal." In triple cocultures of one thalamic explant with a "choice" of two neighboring slices, thalamic axons will not invade slices of cerebellum but behave indistinguishably in response to slices from any region of the hemisphere. Thus the initial tangential distribution of the thalamic projection in vivo (which is achieved by about E16) is unlikely to be controlled by regional variation in signals produced by the cortex. When cortical slices were precultured alone for 7-14 days before the addition of an explant of embryonic thalamus for 4 further days of coculture, the pattern of innervation was more appropriate to the chronological age of the slice than the age at which it was first taken. Thus the timing of the cascade of cortical properties is at least partly intrinsically determined. This sequence of expression of these signals suggests that they play a part in vivo in controlling the outgrowth of thalamic fibers, their accumulation under the cortical plate, their invasion of the plate, and their arborization in layer 4.

Animals↗