Glial responses at neuronal synapses and their purinergic modulation
Zusammenfassung der Projektergebnisse
In recent years we and others have established that purinergic receptors play significant and multiple roles in modulating the network in the rat cerebellar cortex. ATP and ADP both enhance the inhibitory synaptic activity and evoke calcium responses in Bergmann glial cells. Both actions are mediated by metabotropic P2Y1 receptors suggesting that glial and neuronal responses are linked, possibly attributable to the release of gliotransmitters, such as e.g. glutamate. In addition, adenosine modulates excitatory and inhibitory synaptic transmission at the parallel fibre-Purkinje neuron synapse and the Golgi cell-Granule cell synapse, respectively. Hence, the release of ATP and its degradation to ADP and adenosine results in a complex network modulation via P1 and P2 receptors. Since active synapses consume a major fraction of the brain energy, and astrocytes are believed to be involved in supplying energy to neurons, we began to study glucose uptake and metabolism in the mouse cerebellum and hippocampus. The fluorescent glucose analogues 2-NBDG and 6-NBDG were used to monitor uptake of glucose into cells (6-NBDG) and glucose metabolism (2-NBDG) by multi-photon laser scanning microscopy. In addition, we have recently obtained the L-glucose isoform 2-NBDLG, which should not be accepted by glucose transporters. Our results indicate that there is significant non-specific uptake of the fluorescent glucose analogues into the cells. Specific uptake and metabolism of fluorescent glucose were considerably larger in astrocytes than in neurons, both in the hippocampus and in the cerebellum, supporting the hypothesis that glial cells are involved in the supply of energetic substrates to neurons.
Projektbezogene Publikationen (Auswahl)
- (2008). New evidence for purinergic signaling in the olfactory bulb: A2A and P2Y1 receptors mediate intracellular calcium release in astrocytes. FASEB J. 22, 2368-2378
Döngi, M., Deitmer, J.W. & Lohr, C.
- (2009). Neuron-glia pH regulation. In: New Encyclopedia of Neuroscience (ed. L.R. Squire), Academic Press, Oxford, Vol. 6, p. 739-747
Deitmer, J.W. & Chesler, M.
- (2009). Suppression of inhibitory input by Al adenosine receptor activation in rat cerebellar granule cells. Neuroscience 162,946-958
Courjaret, R., Tröger, M. & Deitmer, J.W.
- (2010). Glucose and lactate supply to the synapse. Brain Res. Rev. 63,149-159
Barros, L.F. & Deitmer, J.W.
- (2010). Ion changes and signaling in perisynaptic glia. Brain Res. Rev. 63,113-129
Deitmer, J.W. & Rose, C.R.
- (2011). Purinergic modulation of granule cells. Cerebellum
Courjaret, R., Miras-Portugal, M.T. & Deitmer, J.W.
(Siehe online unter https://doi.org/10.1007/s12311-010-0196-3)
