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Biomedical subjects

Georg W Kreutzberg

Publications and source records attributed to Georg W Kreutzberg.

6 recordsLinked to original sources
PubMed2004

Mitochondria in activated microglia in vitro.

In the CNS, microglia become activated, i.e. change their functional state and phenotype, in response to a wide variety of pathological stimuli. Since this activation is triggered at a very low threshold and at the same time remains territorially restricted, the spatial distribution of activated microglia can be used as a sensitive, generic measure of the anatomical localisation of ongoing disease processes. One protein complex, undetectable in resting microglia but highly up-regulated upon activation in vivo and in vitro, is the 'peripheral benzodiazepine binding site', as measured by binding of the isoquinoline derivate PK11195. Particularly numerous in the outer membrane of mitochondria, this binding site has also been referred to as the 'mitochondrial benzodiazepine receptor'. The de novo expression of this receptor by activated microglia suggests that the process of activation may be associated with important qualitative changes in the state of mitochondria. Here, we provide confocal light- and electron microscopic evidence that the activation of microglia indeed entails conspicuous mitochondrial alterations. In cultured rat microglia stained with the fluorescent probe, JC-1, a sensitive indicator of mitochondrial membrane potential, we demonstrate that stimulation by bacterial lipopolysaccharide and interferon-gamma increases the number of microglial mitochondrial profiles and leads to marked changes in their morphology. Prominent elongated, "needle-like" mitochondria are a characteristic feature of activated microglia in vitro. Electron microscopically, an abundance of abnormal profiles, including circular cristae or ring- and U-shaped membranes, are found. Our observations support the notion that the previously reported increase in microglial binding of PK11195, that labelled with carbon-11 ([11C] (R)-PK11195) has clinical use for the visualisation of activated microglia in vivo by positron emission tomography, may at least in part relate to an increased number and altered functional state of microglial mitochondria.

Animals↗
PubMed2003

Neuregulin-1 isoforms are differentially expressed in the intact and regenerating adult rat nervous system.

Our knowledge on Neuregulin-1 (Nrg-1) during development of the nervous system is increasing rapidly, but little is known about Nrg-1-ErbB signaling in the adult brain. Nrg-1 is involved in determination, proliferation, differentiation, and migration of neurons and glial cells in the developing brain. In the peripheral nervous system, Nrg-1 signaling is required for Schwann cell differentiation and myelination, and establishment of neuromuscular junctions (NMJs). Multiple alternative splicing of Nrg-1 was shown, but correlation of its structural and functional diversity was rarely addressed. Therefore, we investigated the expression of Nrg-1 isoforms in the rat brain and brain-derived cell types, and their involvement in regeneration of the adult brain, using immunohistochemistry, in situ hybridization, and semiquantitative RT-PCR. We found expression of at least 12 distinct Nrg-1 isoforms in the brain and altered expression of several isoforms in the facial motor nucleus after peripheral transection of the seventh cranial nerve. An upregulation of Nrg-1 type-I mRNA, probably type- I-alpha, was observed in reactive astrocytes of the facial nucleus 1 d postaxotomy. Nrg-1 type-III and the splice variants beta1 and beta5 are dramatically downregulated in axotomized motoneurons, which lack contact to their target tissue. Baseline expression levels were reestablished when the first axons reached the facial muscles and reformed NMJs. Nrg-1-beta1 and -beta5 might act in maintenance of NMJs. The splice variants beta2 and beta4 display an initial downregulation of mRNA levels, followed by an increase during the period of axon remyelination. Thus, Nrg- 1-beta2 and -beta4 might be involved in myelination.

Alternative Splicing↗
PubMed2002

Microglia in brain tumors.

Microglia have long been ignored by neurooncologists. This has changed with the realization that microglial cells not only occur within and around brain tumors but also contribute significantly to the actual tumor mass, notably in astrocytic gliomas. In addition, it has been speculated that microglia could play a role in the defense against neoplasms of the nervous system. However, the biological success of these tumors, i.e., their highly malignant behavior, indicates that natural microglial defense mechanisms do not function properly in astrocytomas. In fact, there is evidence that microglial behavior is controlled by tumor cells, supporting their growth and infiltration. This unexpected "Achilles heel" of microglial immune defense illustrates the risk of generalizing on the basis of a single aspect of microglial biology. Microglia are highly plastic cells, capable of exerting cytotoxic functions under conditions of CNS infections, but not necessarily during glioma progression. Thus, the suggestion that microglial activation through stimulation by cytokines (e.g., interferon-gamma) will benefit patients with brain tumors could prove fatally wrong. Therapeutic recruitment of microglia to treat such diffusely infiltrative brain tumors as astrocytic gliomas must be considered premature.

Antigen Presentation↗