Adenosine A(2A) receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus.
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 A(2A) receptors (A(2A)Rs) has been recently reported. In the present paper, we evaluated the role of A(2A)Rs in mediating functional effects of BDNF in hippocampus using A(2A)R 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(2A)Rs abolished BDNF-induced increase of the fEPSP slope in slices from A(2A)R KO mice The reduced functional ability of BDNF in A(2A)R KO mice was correlated with the reduction in hippocampal BDNF levels. In agreement, the pharmacological blockade of A(2)Rs by systemic ZM 241385 significantly reduced BDNF levels in the hippocampus of normal mice. These results indicate that the tonic activation of A(2A)Rs is required for BDNF-induced potentiation of synaptic transmission and for sustaining a normal BDNF tone in the hippocampus.
Tebano
M T
MT
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy. tebano@iss.it
Martire
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Potenza
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Grò
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Pepponi
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Armida
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Domenici
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Schwarzschild
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Chen
J F
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D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques / Q000379:methods; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385