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N Stefanova

Publications and source records attributed to N Stefanova.

14 recordsLinked to original sources
PubMed2002

Ultrastructure of alpha-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells.

Abnormal alpha-synuclein-positive glial cytoplasmic inclusions are found in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. We have recently developed an in vitro model of alpha-synuclein-immunoreactive aggregations in U373 astrocytoma cells. We have additionally overexpressed wild-type and a C-terminally truncated form of alpha-synuclein in primary rat glial cells. Astrocytes and oligodendrocytes were found to form alpha-synuclein-positive aggregations in vitro perinuclearly or in the processes of the cells. The morphological studies presented here demonstrate that the aggregations we have observed in vitro are not limited by a membrane but have unclear borders. They have an amorphous dense core that is intensely alpha-synuclein-immunopositive and a predominantly filamentous halo around. Mainly filamentous structures at the border area between the halo and the core are alpha-synuclein-immunoreactive. We conclude that this in vitro model of alpha-synuclein-positive glial aggregations mimics the morphology of the abnormal glial inclusions described in neurodegenerative disorders and could be a suitable model for studying their role in the pathogenesis of these diseases.

Animals↗
PubMed2001

Glial cell death induced by overexpression of alpha-synuclein.

alpha-Synuclein is present in intracellular protein aggregates that are hallmarks of common neurodegenerative disorders including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. alpha-Synuclein is localized in neurons and presynaptic terminals. Under pathological conditions, however, it is also found in glia. The role of alpha-synuclein in glial cells and its relevance to the molecular pathology of neurodegenerative diseases is presently unclear. To investigate the consequence of alpha-synuclein overexpression in glia, we transfected U373 astrocytoma cells with vectors encoding wild-type human alpha-synuclein or C-terminally truncated synuclein fused to red fluorescent protein. alpha-synuclein immunocytochemistry of transfected astroglial cells revealed diffuse cytoplasmic labeling associated with discrete inclusions both within cell bodies and processes. Susceptibility to oxidative stress was increased in astroglial cells overexpressing alpha-synuclein, particularly in the presence of cytoplasmic inclusions. Furthermore, overexpression of alpha-synuclein induced apoptotic death of astroglial cells as shown by TUNEL staining. Our in vitro model is the first to replicate salient features of the glial pathology associated with alpha-synucleinopathies. It provides a simple testbed to further explore the cascade of events that leads to apoptotic glial cell death in some of these disorders; it may also be useful to assess the effects of therapeutic interventions including antioxidative and antiapoptotic strategies.

Apoptosis↗
PubMed2001

Multiple system atrophy.

Multiple system atrophy (MSA) is an adult-onset sporadic progressive neurodegenerative disorder of unknown etiology. It is clinically characterized by the variable combination of autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs. The present review summarizes up-to-date knowledge on the clinical diagnosis and molecular pathology of MSA. We also review the role of additional investigations that may support a clinical diagnosis of MSA. Finally, we briefly discuss the management of MSA, focusing on possible future therapeutic strategies.

Central Nervous System↗
PubMed2000

Failure of neuroprotection by embryonic striatal grafts in a double lesion rat model of striatonigral degeneration (multiple system atrophy).

In the present experiment we studied the ability of embryonic striatal grafts to protect against striatal quinolinic acid (QA)-induced excitotoxicity in a previously established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA). Male Wistar rats received under halothane inhalation anesthesia a 6-hydroxydopamine 6-OHDA injection into the left medial forebrain bundle. Four to 5 weeks later apomorphine-induced rotation behavior was tested. Rats were divided into two treatment groups receiving either embryonic striatal cell suspensions or sham injections. Apomorphine-induced rotation behavior was retested 2 and 4 weeks after the grafting procedure. Following the rotation test animals of the striatal and sham graft group received a stereotaxic injection of 150 nmol QA. Again rotation behavior was assessed 2 and 4 weeks after lesioning. Brains were then processed to dopamine reuptake ([(3)H]mazindol), dopamine D1 ([(3)H]SCH23390), and D2 ([(3)H]spiperone) receptor autoradiography. Gliosis was detected using [(3)H]PK11195, a marker for peripheral benzodiazepine binding sites. Behavioral and autoradiographic analysis failed to show striatal protection in 6-OHDA prelesioned animals receiving embryonic striatal grafts. These findings indicate that beneficial protective effects of striatal grafts implanted into host striatum prior to excitotoxic insults are abolished in the presence of severe dopaminergic denervation. Our present results are relevant to future applications of neural grafting in MSA-SND.

Animals↗
PubMed2000

Sexual dimorphism of the bed nucleus of the stria terminalis and the amygdala.

The present review summarizes the up-to-date knowledge on the sexual dimorphism of the CNS with special regard to the sexual differentiation of the bed nucleus of the stria terminalis (BST) and the amygdala in rat. The authors provide new evidence for the sexual dimorphism and differentiation of GABAergic, leucine-enkephalin-containing and parvalbumin-immunoreactive neurons in the BST and the amygdala of the rat. Together with testing the gender differences, age-related changes in numbers of the neuronal subpopulations, mentioned above are followed. The authors' results provide morphological and immunocytochemical data that may be used for further studies on sexually dimorphic circuitry and its functional significance.

Amygdala↗
PubMed2000

Depression in alpha-synucleinopathies: prevalence, pathophysiology and treatment.

Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are increasingly recognized as alpha-synucleinopathies, i.e. neurodegenerative disorders that share a common subcellular pathology characterized by alpha-synuclein abnormal aggregation. In the present review we focus on depression in alpha-synucleinopathies, discussing epidemiological, pathophysiological and treatment aspects of this frequently disabling clinical feature which may occur in PD, DLB and MSA alike.

Animals↗
PubMed2000

The predictability of inferior medial canthus as a stable external vertical reference point in maxillary repositioning surgery.

The purpose of this study was to investigate the predictability of using the inferior medial canthus as a stable external reference point for establishment of the vertical dimension in maxillary orthognathic surgery. Ten consecutive patients with skeletal Class II malocclusion and open bite who underwent orthognathic reconstructive surgery were included in the study. Prediction tracings were completed preoperatively and superimposed on an immediate postoperative lateral cephalometric radiograph. In 7 patients, the vertical positioning of the maxillary incisal edge on the immediate postoperative lateral cephalometric radiograph showed no difference from the superimposed preoperative prediction tracing. One patient showed 1 mm difference and 2 patients showed 2 mm difference from the preoperative prediction tracings. All cases resulted in acceptable maxillary incisal exposure relative to upper lip stomion. It is concluded that the inferior medial canthus can be used as a reproducible external vertical reference for orthognathic surgery when the technique described herein is used.

Centric Relation↗
PubMed2000

Predictability of bimaxillary orthognathic surgery using "piggyback" intermediate splints.

Ten consecutive patients underwent bimaxillary surgery including segmental Le Fort I and bilateral sagittal split ramus osteotomies. All 10 patients were symmetric skeletal Class II malocclusion with an anterior open bite. Asymmetry cases were excluded. Dimensional changes depicted on the cephalometric prediction tracing were reproduced in the model surgery and then transferred to the patient during the operative procedure using a "piggyback" intermediate splint. All dimensional changes, except vertical, were transferred from the model surgery to the patient intraoperatively by using a "piggyback" intermediate splint. The accuracy of this transfer and final skeletal result was examined. All the data clearly showed that in no case was any discrepancy greater than 2 mm, which demonstrates the predictable results that can be achieved by using a "piggyback" intermediate splint in bimaxillary orthognathic surgery.

Cephalometry↗
PubMed1999

Geometric considerations when planning an asymmetric genioplasty.

The sliding osteotomy of the inferior border of the mandible, otherwise known as genioplasty, has often been described in the world literature with regard to diagnosis and treatment planning. However, the treatment of the asymmetric chin has received little attention. Moreover, diagnosis and treatment planning of asymmetric chins with concomitant orthognathic surgery is completely lacking from the literature. The complexity of surgically correcting asymmetric chins, compounded with complex, bimaxillary orthognathic surgery, is an extremely challenging task. This article looks at geometric considerations when planning the surgical correction of an asymmetric chin following a protocol of data collection, model surgery, diagnosis, and treatment planning. Clinical experience in the form of a case presentation will demonstrate the millimetric precision that can be achieved when planning corrective genioplasty in an asymmetric patient undergoing concomitant orthognathic surgery.

Adolescent↗
PubMed1998

Gamma-aminobutyric acid-immunoreactive neurons in the amygdala of the rat - sex differences and effect of early postnatal castration.

The distribution of GABA-immunoreactive neurons in the rat amygdala was determined by immunohistochemical methods. Sex differences in the number of GABA-immunoreactive cell bodies were observed in the medial, central, cortical and basolateral amygdaloid nuclei. Females had more numerous GABA-expressing neurons than males (P < 0.01). Castration of neonatal males had controversial effects on this sex difference in the different parts of the amygdaloid complex. In the cortical and basolateral amygdala castrated males showed a female pattern of GABA-expression. In the central amygdala no effect of castration on the number of GABA-immunoreactive cells was found. In the medial amygdaloid nucleus numbers of GABAergic neurons in castrated males differed both from intact males and females. The results of the present study suggest that the expression of GABA in the neurons of the amygdala is under complicated gonadal hormone regulation.

Amygdala↗
PubMed1998

Sex and age differences of neurons expressing GABA-immunoreactivity in the rat bed nucleus of the stria terminalis.

Neurons, containing GABA were visualised immunohistochemically in the bed nucleus of the stria terminalis. Young prepubertal (20 days of age) and postpubertal (3 months and 1 year of age) Sprague-Dawley rats were used. Quantitative studies revealed greater density of GABA-immunoreactive perikarya in female than in male bed nucleus of the stria terminalis. This difference was not due to distribution in different volumes, since the volumes of the bed nucleus of the stria terminalis in the three ages studied did not differ by gender. Castration of new-born male rats caused elevation of the density of GABA-immunoreactive neurons in the bed nucleus of the stria terminalis to female levels on the third month of life. The percentage of nerve cells, expressing detectable amounts of GABA increased with age in the rat bed nucleus of the stria terminalis. The sexual dimorphism of GABA-immunoreactive neurons in the bed nucleus of the stria terminalis may contribute to the formation of reproductive behavior. The elevation of GABA expression with age might reflect change of the cellular activity in this part of the limbic circuitry.

Age Factors↗
PubMed1997

Distribution of GABA-immunoreactive nerve cells in the bed nucleus of the stria terminalis in male and female rats.

The distribution of GABA-immunoreactive neurons in the subnuclei of the rat bed nucleus of the stria terminalis (BST) was studied by means of GABA immunohistochemistry. For detection of GABA immunoreactivity we used polyclonal antibodies and silver intensification. We have compared the pattern of distribution of immunoreactive cells in male and female rats and found some sexual difference, that may underlie functional variety. Computer assisted quantitative analysis of GABA-immunoreactive neurons per mm2 showed statistically significant sex differences in the medial part of the BST (0.001 < P < 0.01). The difference in the BST as a whole was set at 0.05 < P < 0.1. Females had more numerous GABA-immunoreactive cells than males. The measuring of sex differences was done using double-tailed Student's t-test after submitting the data to ANOVA.

Analysis of Variance↗
PubMed1979

Recognition of changes in the dimensions and categories of visual objects.

The aim of the present work is a comparison between recognition with changes in the dimensions of the objects and recognition with changes in the category of the objects. After preliminary training under tachistoscopic ocnditions, to a control set of different contour drawings are added: (1) the same drawings increased or desreased several times; (2) different new drawings with the same size. The percentage of recognized drawings is determined for such exposure time which is needed for the recognition of 60--80 per cent of the drawings in the control set. Recognition is found to be deteriorated in the case of changes both in the dimensions and in the category of the objects, the deterioration being double for the objects with changed category. This fact serves as a basis for rejecting the hypothesis that considerable changes in the dimensions could create new objects for the visual system. It was also found that recognition of pre-trained drawings is either not influenced or comparatively least influenced by the changes in the dimensions and categories. This result is probably due to the specificity of recognition of long trained objects. The results obtained do not contradict the assumption of the participation of spatial consecutive scanning of the iconic memory in the recognition of the spatial properties of visual objects.

Form Perception↗