PMID- 23567067 OWN - NLM STAT- MEDLINE DCOM- 20131126 LR - 20220309 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 709 IP - 1-3 DP - 2013 Jun 5 TI - Modulatory effects of the novel TrkB receptor agonist 7,8-dihydroxyflavone on synaptic transmission and intrinsic neuronal excitability in mouse visual cortex in vitro. PG - 64-71 LID - S0014-2999(13)00262-8 [pii] LID - 10.1016/j.ejphar.2013.03.044 [doi] AB - 7,8-Dihydroxyflavone (7,8 DHF) is a new recently identified TrkB receptor agonist, which possesses a potent neurotrophic activity and shares many physiological properties with the neurotrophin "Brain Derived Neurotrophic Factor" (BDNF). However, its precise mechanism of action at the cellular level has not been clarified yet. In the present study we explored the effects of this agent on synaptic and intrinsic neuronal properties by performing whole-cell patch clamp recordings from layer 2/3 pyramidal neurons. Incubation of acute cortical slices with 7,8-DHF (20 microM) for 30 min caused a selective reduction in the strength of GABAergic inhibition. The amplitude of evoked inhibitory postsynaptic currents (eIPSCs) was significantly reduced to 48.2+/-8.9% of the control level. This might be a result of decreased presynaptic gamma-aminobutyric acid (GABA) release, as suggested by the reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) (control: 10.7+/-0.7 Hz, 7,8 DHF: 7.9+/-0.6 Hz) and increased Paired-Pulse Ratio (PPR) (50+/-8.9%). Conversely, the glutamatergic transmission was unaffected. Moreover, 7,8-DHF was able to alter the intrinsic neuronal excitability, by significantly increasing spike frequency and input resistance (control: 243.75+/-23.4 MOmega, 7,8 DHF: 338.5+/-25.1 MOmega). Remarkably, all reported effects were abolished in presence of the TrkB receptor antagonist K252a indicating a direct involvement of TrkB receptors in the action of 7,8-DHF. These data indicate that 7,8-DHF might be one promising candidate for the development of a new class of drugs called "BDNF mimetics" for the future treatment of cognitive disorders and neurodegenerative diseases. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Marongiu, Daniele AU - Marongiu D AD - Institute of Physiology and Pathophysiology, University Medical Center of the Johannes-Gutenberg University Mainz, Duesbergweg 6, D-55128 Mainz, Germany. FAU - Imbrosci, Barbara AU - Imbrosci B FAU - Mittmann, Thomas AU - Mittmann T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130406 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (6,7-dihydroxyflavone) RN - 0 (Flavones) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Nootropic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Receptors, GABA-A) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Cells, Cultured MH - Electric Impedance MH - Evoked Potentials, Visual/drug effects MH - Flavones/antagonists & inhibitors/*pharmacology MH - GABA-A Receptor Antagonists/pharmacology MH - GABAergic Neurons/*drug effects/metabolism MH - In Vitro Techniques MH - Kinetics MH - Mice MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/*agonists/antagonists & inhibitors/metabolism MH - Neural Inhibition/drug effects MH - Neuroprotective Agents/antagonists & inhibitors/*pharmacology MH - Nootropic Agents/antagonists & inhibitors/pharmacology MH - Protein Kinase Inhibitors/pharmacology MH - Pyramidal Cells/cytology/drug effects/metabolism MH - Receptor, trkB/*agonists/antagonists & inhibitors/metabolism MH - Receptors, GABA-A/chemistry/metabolism MH - Synaptic Transmission/*drug effects MH - Visual Cortex/*drug effects/metabolism EDAT- 2013/04/10 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/04/10 06:00 PHST- 2012/09/18 00:00 [received] PHST- 2013/03/27 00:00 [revised] PHST- 2013/03/28 00:00 [accepted] PHST- 2013/04/10 06:00 [entrez] PHST- 2013/04/10 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - S0014-2999(13)00262-8 [pii] AID - 10.1016/j.ejphar.2013.03.044 [doi] PST - ppublish SO - Eur J Pharmacol. 2013 Jun 5;709(1-3):64-71. doi: 10.1016/j.ejphar.2013.03.044. Epub 2013 Apr 6.