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Proc Natl Acad Sci U S A
2005 Feb 01;1025:1667-72. doi: 10.1073/pnas.0409442102.
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BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes.
Palma E, Torchia G, Limatola C, Trettel F, Arcella A, Cantore G, Di Gennaro G, Manfredi M, Esposito V, Quarato PP, Miledi R, Eusebi F.
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Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABAA receptors, and we have shown previously that the "epileptic receptors" (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the "GABA currents" (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant alpha1beta2gamma2 GABAA receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC.
Binder,
BDNF and epilepsy: too much of a good thing?
2001, Pubmed
Binder,
BDNF and epilepsy: too much of a good thing?
2001,
Pubmed Binder,
The role of BDNF in epilepsy and other diseases of the mature nervous system.
2004,
Pubmed Brandon,
GABAA receptor phosphorylation and functional modulation in cortical neurons by a protein kinase C-dependent pathway.
2000,
Pubmed Brandon,
Receptor for activated C kinase-1 facilitates protein kinase C-dependent phosphorylation and functional modulation of GABA(A) receptors with the activation of G-protein-coupled receptors.
2002,
Pubmed Brünig,
BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA(A) receptor surface expression.
2001,
Pubmed Chang,
Desensitization mechanism of GABA receptors revealed by single oocyte binding and receptor function.
2002,
Pubmed
,
Xenbase Cheng,
Brain-derived neurotrophic factor attenuates mouse cerebellar granule cell GABA(A) receptor-mediated responses via postsynaptic mechanisms.
2003,
Pubmed Danzer,
Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells.
2004,
Pubmed Du,
Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system.
2004,
Pubmed
,
Xenbase Eide,
Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling.
1996,
Pubmed
,
Xenbase Frerking,
Brain-derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus.
1998,
Pubmed Huang,
Trk receptors: roles in neuronal signal transduction.
2003,
Pubmed Huang,
Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role of protein tyrosine phosphorylation and calcineurin.
1998,
Pubmed Jones-Davis,
GABA(A) receptor function and pharmacology in epilepsy and status epilepticus.
2003,
Pubmed Jovanovic,
Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability.
2004,
Pubmed Kneussel,
Receptors, gephyrin and gephyrin-associated proteins: novel insights into the assembly of inhibitory postsynaptic membrane specializations.
2000,
Pubmed Kovalchuk,
Postsynaptic Induction of BDNF-Mediated Long-Term Potentiation.
2002,
Pubmed Koyama,
Brain-derived neurotrophic factor induces hyperexcitable reentrant circuits in the dentate gyrus.
2004,
Pubmed Levine,
Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.
1995,
Pubmed Li,
Enhancement of neurotransmitter release induced by brain-derived neurotrophic factor in cultured hippocampal neurons.
1998,
Pubmed Manabe,
Does BDNF have pre- or postsynaptic targets?
2002,
Pubmed Marsal,
Incorporation of acetylcholine receptors and Cl- channels in Xenopus oocytes injected with Torpedo electroplaque membranes.
1995,
Pubmed
,
Xenbase Miledi,
A calcium-dependent transient outward current in Xenopus laevis oocytes.
1982,
Pubmed
,
Xenbase Miledi,
Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes.
2004,
Pubmed
,
Xenbase Miledi,
Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes.
2002,
Pubmed
,
Xenbase Mizoguchi,
The action of BDNF on GABA(A) currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons.
2003,
Pubmed Mizoguchi,
A rapid increase in the total number of cell surface functional GABAA receptors induced by brain-derived neurotrophic factor in rat visual cortex.
2003,
Pubmed Murray,
Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy.
2000,
Pubmed Palizvan,
Brain-derived neurotrophic factor increases inhibitory synapses, revealed in solitary neurons cultured from rat visual cortex.
2004,
Pubmed Palma,
Threonine-for-leucine mutation within domain M2 of the neuronal alpha(7) nicotinic receptor converts 5-hydroxytryptamine from antagonist to agonist.
1996,
Pubmed
,
Xenbase Palma,
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
2004,
Pubmed
,
Xenbase Patapoutian,
Trk receptors: mediators of neurotrophin action.
2001,
Pubmed Reibel,
Brain-derived neurotrophic factor delays hippocampal kindling in the rat.
2000,
Pubmed Rivera,
BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion.
2002,
Pubmed Takahashi,
Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y.
1999,
Pubmed Tigyi,
A serum factor that activates the phosphatidylinositol phosphate signaling system in Xenopus oocytes.
1990,
Pubmed
,
Xenbase Vial,
G-protein-coupled receptor regulation of P2X1 receptors does not involve direct channel phosphorylation.
2004,
Pubmed
,
Xenbase Xu,
The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes.
2004,
Pubmed Yan,
Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system.
1997,
Pubmed Zhu,
Brain-derived neurotrophic factor enhances fast excitatory synaptic transmission in human epileptic dentate gyrus.
2001,
Pubmed
