LVR-Klinikum Düsseldorf Hospital of the Heinrich-Heine University ...

cells, the cultivation of which was an important component
of the experimental investigations, the disorder-dependent
dysregulation of the cytosolic glucocorticoid receptor in
affective disorders, the intracellular transport of clozapine
via the vesicular monoamine transporters and additionally
apoptotic mechanisms of neutrophil granulocytes involved in
clozapine-induced agranulocytosis could be characterised in
more detail. In addition to the investigations in neuronal and
glial tumour cells, the laboratory has started to isolate and
cultivate native neurones, astrocytes and stem cells from
the CNS of mice. The aim of these experiments is, amongst
other things, to test in how far the in vitro survival rates of
such cells depend on the neuronal/glial composition and in
how far drug components influence cell activity by promoting
or restricting cell vitality. In addition, in order to be able to
represent the electrophysiological activity of neurones in
vitro, the so-called Multi-Electrode-Array (MEA) technique
was established. This provides the experimental opportunity
to model the spontaneous excitation in native neuronal
cells as a correlate of neuronal-glial networks in vitro. By
using this investigation technique, a lesion model will be
created which can be used to investigate mechanisms of cell
damage (whether physically through oxygen withdrawal or
chemically through incubation with neurotoxic substances).
It appears especially interesting to investigate in how far
a reversal of cell damage can be achieved through certain
psychotropic drugs.
Cooperation
s M. Dihné, Department of Neurology,
Heinrich-Heine University, Düsseldorf
s K. Hemmrich, Department of Plastic Surgery,
RWTH Aachen
s M. Jäger, Department of Orthopaedia,
Heinrich-Heine University Düsseldorf
s G. Kobbe, Department of Haematology, Oncology and
Departmental Immunology, Heinrich-Heine University,
Düsseldorf
s V. Kolb-Bachofen, Immunobiological Research Group
for Molecular Medicine, Biological-Medical Research
Center, Heinrich-Heine University, Düsseldorf
s T. Königshausen, Sana Hospital, Düsseldorf
s M. Nöthen, Institute of Human Genetics at the
University of Bonn
s P. Sand, Molecular Genetics Laboratory, Department
of Psychiatry and Psychotherapy, University of
Regensburg
s O. Sergeeva, Institute for Neuro- and Sensory
Physiology, Heinrich-Heine University, Düsseldorf
ReseaRch
s H. Willenberg, Department of Endocrinology,
Diabetology and Rheumatology, Heinrich-Heine
University, Düsseldorf
s J. Wiltfang, LVR-Klinikum, Essen, Department of
Psychiatry and Psychotherapy, University of Duisburg-
Essen
Projects
Enhanced glucocorticoid receptor down-regulation in
immortalised B-lymphocytes of persons with mental
disorders versus healthy controls as parameters for
stress-related disorders
U. Henning, K. Krieger, C. Luckhaus, A. Klimke
in cooperation with M. Nöthen (Bonn)
Project period: 2000–2005
Financing: Departmental research budget
A dysregulation of glucocorticoid-dependent functions
has been described for patients with affective psychoses.
The disorder is characterised by an over-activity of the
hypothalamic-pituitary-adrenocortical axis, which results in
the increased secretion of cortisol into the blood. Cortisol
receptors are not only expressed in the central nervous
system, they are also present in many other organs. The
receptors are also found on peripheral blood cells and
transformed B-lymphoblasts. As a peripherally accessible
in vitro cell model, the number of glucocorticoid receptors
on B-lymphoblasts of the family members of large Spanish
families with hereditary depression was quantified. In cell
culture, there is a significant difference in the quantity
(Bmax) of the glucocorticoid receptors between the
B-lymphoblasts of patients with Major Depression (MD)
and those of healthy controls: a significantly higher number
of receptors was measured in persons with MD (Bmax =
985.2 ± 342.3 fmol/mg protein) than in controls (Bmax =
576.9 ± 190.3 fmol/mg protein). After a short incubation of
the B-lymphoblasts over 48 hours with hydrocortisone (0.1
µM), a stronger down regulation of the cytosolic receptors
(32.9 ± 7.5 %, n = 14) was measured in family members
with affective psychoses than in healthy controls (45.8 ± 8.2
%, n = 13). The regulation of the glucocorticoid system of
the lymphoblasts, measurable as an indicator and termed
“regulative tolerance”, represents an individually constant
trait characteristic that is influenced neither by the evolution
of the disorder nor by the medical treatment of the person.
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