Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons

Using the patch-clamp technique, we studied the modulation of ionotropic g-aminobutyric acid (GABA) and glutamate neurotransmissionby apigenin, a flavonoid with sedative and antidepressant activity. Apigenin reversibly reduced GABA-evoked currents mediated by a1h2g2receptors expressed in HEK293 cells. Amplitude and frequency of spontaneous postsynaptic inhibitory currents (sIPSCs) mediated byGABAA receptors were also decreased by apigenin in cultured cortical neurons. The flavonoid was almost inactive on a-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) mediated currents while it reduced N-methyl-d-aspartate (NMDA) receptor mediated responses witha half maximal inhibiting concentration (IC50) of 10 AM. The flavonoid inhibited also peak amplitude and frequency of spontaneouspostsynaptic excitatory currents (sEPSCs). Finally, apigenin is neuroprotective against glutamate-induced neurotoxicity in cerebellar andcortical neurons in culture. Our data reveal the antagonistic effect of apigenin on GABA and NMDA channels. While the inhibition onGABA receptor cannot explain the effects of the drug in vivo our data on NMDA channels reveal a new target of apigenin. A reduction of thenetwork excitability could thus account for the sedative effects. Furthermore, our data suggest a potential neuroprotective activity of apigenin.D 2004 Elsevier B.V. All rights reserved.