BDNF-TrkB signaling interacts with the GABAergic system to inhibit rhythmic swallowing in the rat.
Brain-derived neurotrophic factor (BDNF) acts as an anorexigenic factor in the dorsal vagal complex (DVC) of the adult rat brain stem. The DVC contains the premotoneurons controlling swallowing, a motor component of feeding behavior. Although rats with transected midbrain do not seek out food, they are able to swallow and to ingest food. Because BDNF and tropomyosin-related kinase B (TrkB) receptors are expressed in the DVC, this study hypothesized that BDNF could modify the activity of premotoneurons involved in swallowing. Repetitive electrical stimulation of the superior laryngeal nerve (SLN) induces rhythmic swallowing that can be recorded with electromyographic electrodes inserted in sublingual muscles. We show that a microinjection of BDNF in the swallowing network induced a rapid, transient, and dose-dependant inhibition of rhythmic swallowing. This BDNF effect appeared to be mediated via TrkB activation, since it no longer occurred when TrkB receptors were antagonized by K-252a. Interestingly, swallowing was inhibited when subthreshold doses of BDNF and GABA were coinjected, suggesting a synergistic interaction between these two signaling substances. Moreover, BDNF no longer had an inhibitory effect on swallowing when coinjected with bicuculline, a GABA(A) receptor antagonist. This blockade of BDNF inhibitory effect on swallowing was reversible, since it reappeared when BDNF was injected 15 min after bicuculline. Finally, we show that stimulation of SLN induced a decrease in BDNF protein within the DVC. Together, our results strongly suggest that BDNF inhibits swallowing via modulation of the GABAergic signaling within the central pattern generator of swallowing.
Bariohay
Bruno
B
Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille, CRN2M, Université de la Méditerranée, Université Paul Cézanne, CNRS UMR 6231, USC-INRA 2027, Marseille cedex 20, France.
Tardivel
Catherine
C
Pio
Juliette
J
Jean
André
A
Félix
Bernadette
B
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D003679:Deglutition / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D026121:Indole Alkaloids / Q000494:pharmacology; D007823:Laryngeal Nerves / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D058787:GABA-A Receptor Antagonists; D026121:Indole Alkaloids; D005680:gamma-Aminobutyric Acid; C049985:staurosporine aglycone; D020813:Receptor, trkB; D001640:Bicuculline