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M B Graeber

Publications and source records attributed to M B Graeber.

102 records · Page 6Linked to original sources
PubMed1988

Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells.

Axotomy of the rat facial nerve leads to mitotic divisions of microglial cells without developing into phagocytes. In order to study the functional characteristics of those activated, i.e., proliferating but nonphagocytic, microglia we investigated the expression of monocyte/macrophage antigens by these cells. Our results show that activated microglia lack monocyte/macrophage antigens recognized by the monoclonal antibodies Ox-41, ED1, ED2, and Ki-M2R but express high levels of CR3 complement receptors in situ.

Animals↗
PubMed1988

The microglial cytoskeleton: vimentin is localized within activated cells in situ.

Unlike astrocytes and oligodendrocytes, microglia are extremely plastic making them the chameleon among the glial cells in the CNS. This great mutability of the microglial cell shape suggests the presence of an elaborate cytoskeleton which is demonstrated here by applying a new ultrastructural method. Electron microscopic immunocytochemistry shows the presence of vimentin at intermediate filament sites in reactive microglia stimulated by rat facial nerve axotomy. It is suggested that vimentin-expression may serve as a marker for activated states of microglia, including brain macrophages.

Animals↗
PubMed1988

Delayed astrocyte reaction following facial nerve axotomy.

Transection of the facial nerve causes a rapid increase of glial fibrillary acidic protein in reactive astrocytes and a proliferation of local microglial cells. The latter is associated with a detachment of synaptic terminals from the regenerating motor neurons. About 3 weeks following axotomy the reactive astrocytes begin to form thin, sheet-like lamellar processes which cover virtually all neuronal surfaces. A high 5'-nucleotidase enzymic activity can be demonstrated in the plasma membrane of these thin cell processes. Subsequently, the lamellar processes become arranged in stacks which persist for several months and thus isolate the regenerating motor neurons from their afferent synaptic input. It is speculated that the process may protect the motor neurons during regeneration.

5'-Nucleotidase↗
PubMed1987

Light and electron microscopical immunocytochemistry of 5'-nucleotidase in rat cerebellum.

5'-Nucleotidase in nervous tissue has so far not been localised at the ultrastructural level using immunocytochemical techniques. We have now applied monoclonal antibodies and a polyclonal antiserum raised against this ecto-enzyme and describe the distribution of 5'-nucleotidase antigenicity in rat cerebellum both at the light and electron microscopic levels. Within all cerebellar layers, 5'-nucleotidase immunoreactivity was found on plasma membranes of glial elements, i.e. Bergmann glial cell processes crossing the molecular layer, astrocytic end-feet around blood vessels and glial cell extensions surrounding single Purkinje cells. In the granular layer, 5'-nucleotidase immunoreactivity was present on glial membranes interposed between granule cells. Neuronal cells or processes were devoid of immunoreactivity. The immunocytochemical results were compared with conventional 5'-nucleotidase histochemistry. Both techniques showed the same ecto-localisation of the enzyme and favour the view of 5'-nucleotidase being predominantly situated at glial plasma membranes.

5'-Nucleotidase↗
PubMed1986

Astrocytes increase in glial fibrillary acidic protein during retrograde changes of facial motor neurons.

Concomitant with the proliferation of satellite microglial cells occurring in the process of motor neuron regeneration, an astrocytic hypertrophy is also seen. A remarkable increase of glial fibrillary acidic protein (GFAP) immunoreactivity is demonstrated in astrocytes of the facial nucleus within a few days following nerve transection. The increase of GFAP antigenicity is associated with an increased appearance of glial filaments and astrocytic processes. We suggest that resident protoplasmic astrocytes become involved in retrograde changes in facial motor neurons and transform into reactive astrocytes. They are of the fibrous type and highly positive for GFAP.

Animals↗
PubMedDate not supplied

Microglia only weakly present glioma antigen to cytotoxic T cells.

Microglia and brain macrophages represent a substantial fraction of the cells present in astrocytic gliomas. Yet, the functional role of microglia in these tumors has remained enigmatic. We have compared rat microglial cells and thymocytes with regard to their ability to present purified CNS proteins, MBP and S100beta, as well as C6 glioma cells to specific T lymphocytes. In addition, a new cytotoxicity assay based on fluorescence activated cell sorting of tumor cells carrying the green fluorescent protein was established. This assay was used to determine the influence of microglial population density and activational state on C6 glioma cell survival in vitro. Microglia were consistently found to present MBP and S100beta less efficiently than thymocytes and appeared to be unable to present C6 glioma cells to cytotoxic T lymphocytes. In addition, high concentrations of microglial cells attenuated the cytotoxic effects of these T cells on C6 glioma cells whereas thymocytes significantly supported their specific killing. It is suggested that defense functions of microglial cells against C6 glioma are severely compromised and that the observed deficiency in antigen presentation may play an important role for astrocytoma growth in vivo.

Animals↗
PubMedDate not supplied

Nuclear hormone and orphan receptors: their role in neuronal differentiation and cytoprotection and in the pathogenesis of Parkinson's disease.

Human nuclear hormone receptors (NHR) and orphan receptors (NOR) act as transcription factors in response to a wide range of circulating hormones and unknown ligands. A role for NHR and NOR in disorders of the subcortical dopaminergic pathways such as Parkinson's disease (PD) is suggested by a wealth of recent data including experimental observations. Both classes of receptors promote the formation of specific neuronal identities, tissue patterning during embryonic development and the maturation of vulnerable monoaminergic and cholinergic neurons. NHR and NOR are also known to exert a neuroprotective function on adult neurons. The scope of this review is to revisit the functional profile of these receptors with particular reference to their activity in the development of selected neuronal populations relevant to the pathophysiology of PD and to discuss how they may relate to the neuropathological and clinical expression of the disease.

Animals↗
PubMedDate not supplied

Microglia in culture: what genes do they express?

The cell culture model utilized in this study represents one of the most widely used paradigms of microglia in vitro. After 14 days, microglia harvested from the neonatal rat brain are considered 'mature'. However, it is clear that this represents a somewhat arbitrary definition. In this paper, we provide a transcriptome definition of such microglial cells. More than 7,000 known genes and 1,000 expressed sequence tag clusters were analysed. 'Microglia genes' were defined as sequences consistently expressed in all microglia samples tested. Accordingly, 388 genes were identified as microglia genes. Another 1,440 sequences were detected in a subset of the cultures. Genes consistently expressed by microglia included genes known to be involved in the cellular immune response, brain tissue surveillance, microglial migration as well as proliferation. The expression profile reported here provides a baseline against which changes of microglia in vitro can be examined. Importantly, expression profiling of normal microglia will help to provide the presently purely operational definition of 'microglial activation' with a molecular biological correlate. Furthermore, the data reported here add to our understanding of microglia biology and allow projections as to what functions microglia may exert in vivo, as well as in vitro.

Animals↗
PubMedDate not supplied

Role of mitochondria in Parkinson disease.

The cause of the selective degeneration of nigrostriatal neurons in Parkinson disease (PD) has remained largely unknown. Exceptions include rare missense mutations in the alpha-synuclein gene on chromosome 4, a potentially pathogenic mutation affecting the ubiquitin pathway, and mutations in the parkin gene on chromosome 6. However, unlike classical PD, the latter syndrome is not associated with the formation of typical Lewy bodies. In contrast, a biochemical defect of complex I of the mitochondrial respiratory chain has been described in a relatively large group of confirmed PD cases. Recent cybrid studies indicate that the complex I defect in PD has a genetic cause and that it may arise from mutations in the mitochondrial DNA. Sequence analysis of the mitochondrial genome supports the view that mitochondrial point mutations are involved in PD pathogenesis. However, although mitochondria function as regulators in several known forms of cell death, their exact involvement in PD has remained unresolved. This is of relevance because classical apoptosis does not appear to play a major role in the degeneration of the parkinsonian nigra.

Apoptosis↗
PubMedDate not supplied

[The apolipoprotein E gene and Alzheimer disease phenotype].

The relevance of the apolipoprotein E epsilon 4 allele as risk factor for Alzheimer's disease is independent of age. This was demonstrated in 126 patients and 72 healthy controls. The age in both groups varied between 44 and 95 years. An earlier onset of symptoms among carriers of the epsilon 4 allele, however, was observed only in the oldest patients. This may reflect a selection bias which is due to the association of the epsilon 4 allele with two competitive age-dependent risks: for Alzheimer's disease and for coronary heart disease. In a subsample of 64 patients who had participated in a longitudinal study no relationship was found between the apolipoprotein E genotype and clinical symptoms or symptom progression.

Adult↗
PubMedDate not supplied

Regional heterogeneity of mtDNA heteroplasmy in parkinsonian brain.

There is increasing evidence for a role of defects of mitochondrial DNA in the etiology of neurodegenerative disorders such as Parkinson's and Alzheimer's disease as well as in normal aging. In several studies a biochemical defect of complex I of the respiratory chain (NADH dehydrogenase, EC 1.6.5.3) has been found in the substantia nigra of Parkinsonian brains. Thus, mutations of mitochondrial genes encoding subunits of complex I could contribute to the pathogenesis of Parkinson's disease. A heteroplasmic G5460A mutation affecting the ND2 subunit of NADH dehydrogenase was detected in several brains of patients with idiopathic Parkinson's disease. Since this mutation is heteroplasmic we were interested in the distribution of mutated and wild-type mitochondrial DNA in different brain areas. Relative levels of mutated DNA were quantified in a large number of anatomical regions using DNA extracted from formalin-fixed and paraffin-embedded brain tissue. DNA was amplified by the polymerase chain reaction and digested employing the restriction enzyme Hphl. The proportion of mutated DNA was determined by laser densitometry. In addition, genotype-phenotype analyses were performed on sections of the substantia nigra with the aid of an automated image analysis system. Ratios of mutant to wild-type DNA varied between 44% and 98%. However, there was no systematic relationship between mutated DNA ratios and ontogenetically related brain areas suggesting that the observed regional heterogeneity of mitochondrial DNA heteroplasmy is most likely due to random segregation during development. Therefore, tissue-specific differences in the sensitivity to pathogenic effects of the ND2(5460) mutation or the influence of additional susceptibility genes may be envisioned.

Brain↗