Adenosine A2A receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus

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 A 2A antagonist ZM 241385. Similarly, genetic deletion of the A 2ARs abolished BDNF-induced increase of the fEPSP slope in slices from A2AR KO mice The reduced functional ability of BDNF in A 2AR 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 A 2ARs is required for BDNF-induced potentiation of synaptic transmission and for sustaining a normal BDNF tone in the hippocampus. © 2007 The Authors.