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Our research focuses on two subjects: First,
we try to unravel the molecular and functional design of electrical
synapses (gap junctions) in the central nervous system (CNS). In order
to achieve a better insight into the function of electrotonic coupling
via gap juntions we
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try to clone the channel forming proteins from diverse brain areas, including
the retina, which show a high incidence of coupling,
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study their localization by light and electron microscopical immunocytochemistry
and
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develop functional mutations in tissue cultures and animal models. The
latter approach will help us to understand the communicative properties
of electrical synapses in neuronal networks.
A better knowledge of the function of gap junctions in normal brain tissue
will allow us to understand the contribution of electrical synapses to
diseases of the nervous system in which interneuronal signalling is afflicted;
i.e. epilepsia, Parkinsonism, and defects of memory storage. Since glial
cells also show a high incidence of gap junction coupling we expect information
on pathological mechanisms of the brain in which glial cells are involved;
i.e. brain edema and demyelinating diseases.
Actual Literature (Reviews and Book Articles):
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Dermietzel R. and D.C. Spray: Gap junction in the brain: Why? Where? How
many? Trends Neurosci. 16, 186-192. (1993)
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Spray, D.C. and R. Dermietzel: X-linked dominant Charcot-Marie-Tooth disease
and other potential gap junction
diseases of the nervous system. Trends Neurosci. 18, 256-262 (1995)
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Spray, D., C., Dermietzel, R. (1996) Gap junctions in the nervous system.
R.G. Landes Company, Austin. Available via Amazon.com.
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Dermietzel R.: Gap junction wiring: a new principle in cell-to-cell communication
in the nervous system. Brain Res.
Rev. 26, 176-183 (1998)
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Dermietzel R, Spray D C: From Neuro-Glue (Nervenkitt) to Glia: A Prologue.
Glia 24, 1-7 (1998)
The second topic of our research is the
blood-brain-barrier
(BBB). The BBB constitutes a structural and metabolic barrier between the
intravascular compartment of cerebral blood vessels and the parenchyma
of the brain. The structural constituents of the BBB are provided by interendothelial
tight junctions and a low rate of transcytosis. Specific sets of
transporter, receptors, and enzymes represent the metabolic component.
Thus, the barrier by controlling the exchange between the blood and
the brain tissue, creates the specific environment necessary for
proper brain functioning. The morphogenetic mechanisms which guide the
development of the BBB are essentially unknown. We are currently trying
to establish tissue culture systems in which the development of the
BBB can be mimicked. Such in vitro systems are essential to elucidate the
molecular background of BBB maturation and malfunctioning.
Actual Literature (Reviews and Book Articles):
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Dermietzel, R. and Krause D. (1992). Molecular Anatomy of the Blood-Brain
Barrier as Defined by Immunocytochemistry. Intern. Rev. Cytol.
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Dermietzel, R., Faustmann, P., Krause, D. (1999). Inflammatory reaction
of the blood-brain barrier. Alfred Benzon Symposium 45 (eds. O.B. Paulson,
G.M. Knudsen, T. Moos) Munsgaard, Copenhagen, pp 403-409
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Krause, D., Faustmann, P., Dermietzel, R. (in press) Molecular anatomy
of the blood-brain-barrier in development and aging. Humana Press.
Cooperation / Offers for Cooperation
Partners:
Methods:
The following methods are routinely performed in our laboratories:
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Cell and tissue cultures: Primary astrocytes, microglia, cerebral pericytes
and cerebral endothelial cells.
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Isolation and culturing of cerebral micromicrovessels
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Culturing of organotypic brain slices
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Culturing of Schwann cells and their precursors
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Culturing of various cell lines
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Confocal laser microscopy
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In situ hybridization
Molecular biological techniques
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Cloning from cDNA and genomic libraries
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RT-PCR
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Transfection of GFP tagged connexins
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Point mutations and truncation of connexin genes
Morphological techniques
Methods in preparation
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Lasermicrodissection
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Biolistic transfection techniques
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Conventional light and electron microscopy
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Light and electron microscopical immunochemistry
For an introduction into diverse techniques see: O. v. Bohlen und
Halbach and R. Dermietzel: Methoden der Neurohistologie,
Spektrum Akademischer Verlag, Heidelberg 1999.
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