Biomedical subjects

C Karch

Publications and source records attributed to C Karch.

6 recordsLinked to original sources

PubMed2004

Signalling mechanisms for survival of lesioned motoneurons.

Mechanisms controlling neuronal survival play an important role both during development and after birth, in particular when the nervous system is lesioned. Isolated embryonic motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal cell death during development and under pathophysiological conditions after neurotrauma. These studies have led to the identification of neurotrophic factors which under physiological conditions regulate survival and functional properties, and after neurotrauma promote regeneration and plasticity. Functional analysis of these molecules, in particular by generation of gene knockout mice, has led to a more detailed understanding of complex requirements of individual types of neurons for their survival and also paved the way for a better understanding of the signalling pathways in lesioned neurons which decide on cell death or survival after axotomy and other pathophysiological conditions. These findings could ultimately lead to a rational basis for therapeutic approaches aiming at improving neuronal survival and regeneration after neurotrauma.

Adenosine Monophosphate↗

PubMed2003

[The most common form of dizziness in middle age: phobic postural vertigo].

Up to now, there have been only a few valid epidemiological investigations of dizziness or vertigo as key symptoms. According to an analysis of 4,214 patients examined between 1989 and 2002 in an outpatient dizziness unit, benign peripheral paroxysmal positional vertigo (BPPV) and phobic postural vertigo (PPV) constitute the two most frequent syndromes. In this study, the relative age and sex distribution of both disorders was analysed. In the age group from 20 to 50 years, PPV was comparatively the most frequent form of dizziness, with a share of 22% to 26%. When left untreated, PPV becomes chronic in most cases and leads to considerable impairments, also at work. However, when diagnosed correctly, it can be treated successfully in more than 70% of cases. Thus, it takes on considerable medical and socioeconomic significance and should be part of the diagnostic repertoire of every doctor.

Adult↗

PubMed2002

Human cerebral endothelial cells are a potential source for bioactive BDNF.

Inflammatory stimuli within the central nervous system may not only induce tissue damage but may also convey neuroprotection. It has been shown that brain derived neurotrophic factor (BDNF) is a neuroprotective candidate. Here we show that BDNF is constitutively expressed in cultured human cerebral endothelial cells (HCEC) and can further be upregulated under proinflammatory conditions. TNF-alpha treatment resulted in an increase in BDNF mRNA expression and protein levels were significantly elevated after 72 h (69+/-33%, P<0.01). Using functional assays it was demonstrated that BDNF produced by HCEC is bioactive and supports motoneuron survival. In contrast, BDNF expression was reduced by TNF-alpha in human umbilical vein endothelial cells (HUVEC). We conclude that HCEC likely to contribute to neuronal survival under physiological and inflammatory conditions.

Brain-Derived Neurotrophic Factor↗

PubMed2001

Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons.

Embryonic sensory and motoneurons depend on neurotrophic factors for survival. Here we show that their survival requires B-Raf, which, in this function, cannot be substituted by C-Raf. Sensory and motoneurons from b-raf-deficient mice do not respond to neurotrophic factors for their survival. However, these primary neurons can be rescued by transfection of a b-raf expression plasmid. In contrast, c-raf-deficient neurons survive in response to neurotrophic factors, similarly to neurons from wild-type mice. This points to an essential and specific function of B-Raf in mediating survival of sensory and motoneurons during development.

Animals↗

PubMed2001

Motoneuron cell death and neurotrophic factors: basic models for development of new therapeutic strategies in ALS.

Motoneurons are generated in excess during embryonic development of higher vertebrates. In the lumbar spinal cord of the developing rat, about 6000 motoneurons are present at embryonic day 14. These neurons grow out axons which make contact with their target tissue, the skeletal muscle. About 50% of the motoneurons are lost during a critical period from embryonic day 14 until postnatal day 3. This process, which is called physiological motoneuron cell death, has been the focus of research aiming at the identification of neurotrophic factors which regulate motoneuron survival during this developmental period. Motoneuron cell death can also be observed in vitro when the motoneurons are isolated from the embryonic avian or rodent spinal cord. These isolated motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal degeneration during development and under pathophysiological conditions in neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Accumulating evidence from such studies suggests that some specific requirements of motoneurons for survival and proper function may change during development. These findings might be relevant for understanding the pathophysiological processes underlying ALS and thus could contribute to the development of new therapeutic strategies.

Amyotrophic Lateral Sclerosis↗

PubMed2000

The neuronal apoptosis inhibitory protein suppresses neuronal differentiation and apoptosis in PC12 cells.

The human neuronal apoptosis inhibitory protein (NAIP) gene has been discovered as a candidate gene for spinal muscular atrophy, a genetic disorder characterized by motor neuron loss in the spinal cord. The telomeric NAIP gene on human chromosome 5 is deleted together with survival motor neurons (SMN) in many cases of the most severe forms of the disorder. NAIP, c-IAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP, survivin and Apollon comprise the mammalian inhibitors of the apoptosis family and contain an N-terminal domain with 1-3 imperfect repeats of an approximately 65 amino acids domain named the baculovirus IAP repeat (BIR) motif. We identified six NAIP genes in the mouse genome which were found to be expressed in a broad range of tissues. Furthermore, we have investigated the effects of NAIP in the rat pheochromocytoma PC12 cell line. These cells differentiate in the presence of nerve growth factor (NGF) into cells that resemble sympathetic neurons. We observed that NAIP overexpression impaired NGF-induced neurite outgrowth. The BIR motifs of NAIP (residues 1-345) were not required for this effect. However, the BIR domains of NAIP were essential to prevent apoptosis in PC12 cells after NGF deprivation or TNF-alpha receptor stimulation. Expression of full-length but not BIR-deleted-NAIP protects against cell death. This correlates with reduced activity of the cell death effector protease, caspase-3, in lysates of NAIP-PC12 cells, as measured by cleavage of the fluorogenic tetrapeptide substrate Asp-Glu-Val-Asp. Thus, unregulation of cellular differentiation and/or caspase suppression may contribute to motoneuron dysfunction and cell death in spinal muscular atrophy where NAIP is mutated.

Amino Acid Motifs↗