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- Title
Adenosine A<sub>2A</sub> receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus.
- Authors
Tebano, M. T.; Martire, A.; Potenza, R. L.; Gr, C.; Pepponi, R.; Armida, M.; Domenici, M. R.; Schwarzschild, M. A.; Chen, J. F.; Popoli, P.
- Abstract
Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, enhances synaptic transmission and regulates neuronal proliferation and survival. Both BDNF and its tyrosine kinase receptors (TrkB) are highly expressed in the hippocampus, where an interaction with adenosine A2A receptors (A2ARs) has been recently reported. In the present paper, we evaluated the role of A2ARs in mediating functional effects of BDNF in hippocampus using A2AR knock-out (KO) mice. In hippocampal slices from WT mice, application of BDNF (10 ng/mL) increased the slope of excitatory post-synaptic field potentials (fEPSPs), an index of synaptic facilitation. This increase of fEPSP slope was abolished by the selective A2A antagonist ZM 241385. Similarly, genetic deletion of the A2ARs abolished BDNF-induced increase of the fEPSP slope in slices from A2AR KO mice The reduced functional ability of BDNF in A2AR KO mice was correlated with the reduction in hippocampal BDNF levels. In agreement, the pharmacological blockade of A2Rs by systemic ZM 241385 significantly reduced BDNF levels in the hippocampus of normal mice. These results indicate that the tonic activation of A2ARs is required for BDNF-induced potentiation of synaptic transmission and for sustaining a normal BDNF tone in the hippocampus.
- Publication
Journal of Neurochemistry, 2008, Vol 104, Issue 1, p279
- ISSN
0022-3042
- Publication type
Academic Journal
- DOI
10.1111/j.1471-4159.2007.05046.x