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Volume 7, Issue 6 (Suppl) Clin Exp Pharmacol, an open access journal
ISSN: 2161-1459
Page 12
Notes:
December 14-16, 2017 Rome, Italy
International Conference on
2nd International Conference on &
Toxicology and Clinical Pharmacology
Generic Drugs and Biosimilars
CO-ORGANIZED EVENT
Astrocytes and glutamate in striatum: A2A-D2 receptor-receptor interaction controls glutamate
release from striatal astrocytic processes
In the 1980s, a newmodel of chemical signal recognition/decoding was proposed, according to which integrative information
handling already occurs at membrane level, via receptor-receptor interactions. Specifically, evidence for striatal A2A and D2
receptor-receptor interaction in A2A-D2 heterodimers in striatal neurons, opened new perspectives on the Parkinson's disease
pathophysiology, and provided new targets for anti-parkinsonian drugs. Roles for astrocytes, the most numerous cells in the
nervous system, and relevance of the neuron-astrocyte network function in disease vulnerability are increasingly recognized. In
particular, astrocyte dysfunction at tripartite synapses and altered glutamatergic transmission are emerging in neuropsychiatric
disorders including the Parkinson's disease. Despite the change from a neurocentric to an astrocentric view of neuropsychiatric
disorders, and major attention to striatal A2A and D2 receptors, striatal glial A2A and D2 receptors have so far received
scarce attention. Our findings suggest - combining confocal microscopy and functional neurochemical approaches on purified
preparations of astrocyte processes from adult rat striatum and indicate a crucial integrative role of A2A-D2 circuits at the
plasma membrane of striatal astrocyte processes in the control of glutamatergic transmission. Indeed, we obtained evidence
that: D2 and A2A receptors are expressed in striatal astrocyte processes; D2 receptors inhibit the release of glutamate from
astrocyte processes; astrocytic A2A and D2 receptors can form A2A-D2 heterodimers; homocysteine can reduce D2-mediated
control of astrocytic glutamate release. It is to note that hyperhomocysteinemia has been hypothesized to play roles in tardive
L-dopa side-effects in Parkinson’s patients. Notably, expansion of presynaptic astrocyte processes, and altered neuron-astrocyte
interactions at striatal glutamatergic synapses, have been found in Parkinson's disease. Thus, reduced D2-mediated control at
striatal presynaptic astrocyte processes might result in an increase in synaptic glutamate level and in turn helps understand
how astrocytes (and remodeling of astrocyte processes) contribute to the pathophysiology of Parkinson's disease.
Biography
Manuela Marcoli has completed her MD degree from Pavia University, Italy (PhD. Degree in Clinical Pharmacology from Pavia University, Italy). She is Professor of Phar-
macology at the University of Genova, Italy. She has over 85 publications that have been cited over 1300 times, and her publication H-index is 22 and has been serving
as a Reviewer of reputed Journals.
Manuela Marcoli
University of Genova, Italy
Manuela Marcoli, Clin Exp Pharmacol 2017, 7:6(Suppl)
DOI: 10.4172/2161-1459-C1-024