title: Targeted taste cell-specific overexpression of brain-derived neurotrophic factor in adult taste buds elevates phosphorylated TrkB protein levels in taste cells, increases taste bud size, and promotes gustatory innervation.
abstract: Brain-derived neurotrophic factor (BDNF) is the most potent neurotrophic factor in the peripheral taste system during embryonic development. It is also expressed in adult taste buds. There is a lack of understanding of the role of BDNF in the adult taste system. To address this, we generated novel transgenic mice in which transgene expression was driven by an α-gustducin promoter coupling BDNF expression to the postnatal expression of gustducin in taste cells. Immunohistochemistry revealed significantly stronger BDNF labeling in taste cells of high BDNF-expressing mouse lines compared with controls. We show that taste buds in these mice are significantly larger and have a larger number of taste cells compared with controls. To examine whether innervation was affected in Gust-BDNF mice, we used antibodies to neural cell adhesion molecule (NCAM) and ATP receptor P2X3. The total density of general innervation and specifically the gustatory innervation was markedly increased in high BDNF-expressing mice compared with controls. TrkB and NCAM gene expression in laser capture microdissected taste epithelia were significantly up-regulated in these mice. Up-regulation of TrkB transcripts in taste buds and elevated taste cell-specific TrkB phosphorylation in response to increased BDNF levels indicate that BDNF controls the expression and activation of its high affinity receptor in taste cells. This demonstrates a direct taste cell function for BDNF. BDNF also orchestrates and maintains taste bud innervation. We propose that the Gust-BDNF transgenic mouse models can be employed to further dissect the specific roles of BDNF in the adult taste system.
authors.affiliation: University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee 38163, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Nosrat
authors.forename: Robert F
authors.initials: RF
authors.lastname: Margolskee
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Nosrat
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D058477:Receptors, Purinergic P2X3 / Q000096:biosynthesis / Q000235:genetics; D013650:Taste Buds / Q000378:metabolism*; D055697:Taste Perception; D014059:Tongue / Q000294:innervation* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D020813:Receptor, trkB
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D058477:Receptors, Purinergic P2X3; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB