Biomedical subjects

Michaela Strohschneider

Publications and source records attributed to Michaela Strohschneider.

5 recordsLinked to original sources

PubMed2006

Prominent corticosteroid disturbance in experimental prion disease.

Prion diseases comprise a group of neurodegenerative disorders that invariably lead to death in affected individuals. The most prominent event in these diseases is a rapid and pronounced neuronal loss, although the cause and the precise mechanisms of neuronal cell death have not been identified so far. Recently, it has been suggested that corticosteroids might play a role in the pathogenesis of neurodegenerative disorders in general, as the regulation of these hormones was found to be disturbed in Alzheimer's and Parkinson's disease, as well as in a transgenic mouse model of Alzheimer's disease. To evaluate the possible corticosteroid disturbances in prion diseases, we determined the concentration of corticosterone metabolites in the faeces of scrapie-inoculated mice during the course of the clinical disease. We observed markedly elevated concentrations of the metabolites during the last 5 weeks of the disease, as well as a severe disturbance of circadian periodicity of corticosterone excretion as much as 2 weeks before this elevation. A simultaneous downregulation of cerebral neuronal glucocorticoid receptors was not detectable by immunohistochemistry, indicating that increased corticosteroids can elicit their effects in mouse scrapie freely. The dysregulation of corticosteroid excretion might act as a further cofactor in the pathogenesis of scrapie, for example by preconditioning nerve cells to disease-immanent neurotoxic stimuli, such as oxidative stress, and to apoptosis.

Adrenal Cortex Hormones↗

PubMed2005

Subcellular localization of disease-associated prion protein in the human brain.

Disease-associated prion protein (PrP(TSE)) deposits in distinct immunostaining patterns in the brain in Creutzfeldt-Jakob disease, including synaptic, extracellular, and cell-associated localizations. After having developed an appropriate pretreatment protocol to enhance immunostaining for PrP(TSE) without damaging epitopes of other antigens, we systematically evaluated co-localization patterns of distinct PrP(TSE) immunodeposits by confocal laser microscopy, including optical serial sectioning. As shown by quantification, the most prominent co-localization of PrP(TSE) is with synaptophysin, but PrP(TSE) may also co-deposit with connexin-32, a gap junction-related protein. Furthermore, neuronal cell bodies, dendrites, axons, astrocytes, and microglia harbor granular PrP(TSE) deposits. Highly aggregated deposits are focally ubiquitinated. We conclude that PrP(TSE) is not exclusively associated with chemical but also with electric synapses, axonal transport may be a relevant route of PrP(TSE) spread in the brain, and activated microglia and astrocytes may play a role in PrP(TSE) processing, degradation, or removal.

Brain↗

PubMed2004

The prion protein in human neuromuscular diseases.

The basis of human prion diseases affecting the nervous system is accumulation of a disease-associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non-diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural PrPC-PrPSc conversion. In addition, our observations suggest that PrPC may have a general stress-response effect in various neuromuscular disorders.

Chronic Disease↗

PubMed2004

Complement activation in human prion disease.

The central event in the neuropathological process of prion diseases (PrD) is the accumulation of abnormal prion protein accompanied by severe neuronal loss. Despite the infectious nature of these diseases, no prominent immune response has been detected yet. However, recent studies have shown that complement, a component of the innate immune system, is involved in the early pathogenesis of experimental prion infection. Here we demonstrate, in the diseased human brains, the presence of active compounds of the complement system, like C1q and C3b, in extracellular disease-associated prion protein deposits and the membrane attack complex in neurons. The neuronal localization of the membrane attack complex correlates well with the severity of disease-specific pathology and TUNEL labeling of neurons, irrespective of genotype or molecular phenotype of human prion diseases.

Adolescent↗

PubMed2002

The prion protein in human neurodegenerative disorders.

We evaluate cellular prion protein (PrP(C)) immunoreactivity (IR) in Alzheimer's, Parkinson's, diffuse Lewy body, and motor neuron diseases (MND), progressive supranuclear palsy, and multiple system atrophy. We use immunohistochemistry for PrP, including five monoclonal antibodies against different epitopes and three different pretreatments, alpha-synuclein, phosphorylated tau, beta-amyloid, and ubiquitin. Disease-specific inclusions are devoid of PrP(C) IR. Using double immunofluorescence and confocal laser microscopy we observe focal overlapping of PrP(C) with tau and with alpha-synuclein in early, but not in fully developed inclusions. However, PrP(C) IR neurons may contain abnormal tau or alpha-synuclein aggregates. Additionally, we observe a loss of PrP(C) IR in anterior horn neurons in MND. Our results suggest that expression of PrP(C) reflects a general response to cellular stress rather than specific co-operation in aggregation of other proteins.

Amyloid beta-Peptides↗