Behavioural and in vivo pharmacologyContact:Dr. Ute Krügel |
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Research interests:1. Involvement of metabotropic P2Y receptors in the mediation of cognitive processing and behavioural functions |
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Purines and
pyrimidines are potent extracellular signals acting at cell surface
receptors, at ionotropic P2X and metabotropic P2Y receptors. P2Y
receptors are expressed early in the embryonic brain and are widely
distributed at neurones and glia cells. By activation of different
G-proteins coupled to various signal transduction pathways P2Y
receptors can modulate long lasting trophic effects (e.g. cell
proliferation) or pre- and postsynaptic stimulation with subsequent
release of neurotransmitters or ADP/ATP itself. |
 Social contacts of Wistar (RjHn:WI) rats. |
2. Behavioural conditioning of immune functions - central neurotransmission and peripheral immune regulationThe immune system
can be modified via behavioural conditioning, documenting the
brain’s abilities to sense immune-derived signals or immune
status, to associate them with concurrently relevant exteroceptive
stimuli, and to reinstate such immune responses on demand. Behavioural
conditioned immunosuppressive effects in rats employing cyclsoporine A
as an unconditioned stimulus are clinically relevant since they prolong
heart allograft survival and attenuate allergic responses. These
conditioned effects are mediated centrally via the insular cortex and
the amygdala as well as on the peripheral efference via the splenic
nerve, through noradrenaline and β-adrenoceptor-dependent
mechanisms. 3. Purinergic regulation of food intake – modulation of leptin-mediated anorexiaAnorexia is part of
acute-phase responses to illness and may be deleterious over time.
Behavioural, microdialysis and EEG investigations have shown that
central receptors sensitive to extracellular ATP (P2YRs) are involved
in the regulation of food intake in various brain regions. Leptin is a
possible mediator of anorexia. Central leptin induces hypophagia and a
decrease in extracellular basal and feeding induced dopamine, probably
related to the motivation to take food in. The stimulation of P2Y1Rs
abolished the impairment of leptin-induced feeding pattern mediated by
an increase of dopaminergic signalling. In agreement, we found a
co-localisation of the leptin receptor (ObR) on tyrosine
hydroxylase-positive fibres in the NAc and on cell bodies in the VTA.
By chronic food restriction, the P2YR mRNA expression was increased in
the same time course as the mRNA of the leptin receptor subsequent to a
drop down of plasma leptin, suggested to provide an increase the
mesolimbic sensitivity directed to achieve satisfaction and reward. The
investigations contribute to a better understanding of brain detection
of peripheral metabolic and humoral state. 4. P2 receptors and neuronal injuryExtracellular adenosine 5'-triphosphate (ATP) is an activity-dependent signaling molecule regulating glia-glia and glia-neuron communication. The release of ATP is a widespread physiological process. Further, high excitotoxic amounts of ATP may exit cells through damaged plasma membrane in settings of inflammation, ischemia or mechanical injury. P2 receptor activation could either be a cause or a consequence of neuronal cell death/ glial activation and may result in detrimental and/or beneficial effects. Important P2 receptor-mediated neurodegenerative and neuroprotective processes and their beneficial modulation by therapeutic manipulations are in the focus. Morphological and structural changes of the injured or ischemic brain are under investigation by immunocytochemical methods or MRT. Functional consequences after cortical and subcortical trauma and after occlusion of the arteria cerebri media of rat or transgenic mice are monitored by EEG recording, by motor function and coordination and by cognitive capabilities. The group:Dipl. Biol. Holger Koch (PhD student) |
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Anne-Kathrin Krause |
Lutz Feige |
Holger Koch |
External and local collaborations:Dr. Anton Bespalov, Abbott GmbH & Co. KG,
Ludwigshafen |
