PMID- 22442142 OWN - NLM STAT- MEDLINE DCOM- 20120713 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 20 DP - 2012 May 11 TI - 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. PG - 16791-800 LID - 10.1074/jbc.M111.328476 [doi] AB - 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 alpha-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. FAU - Nosrat, Irina V AU - Nosrat IV AD - University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee 38163, USA. FAU - Margolskee, Robert F AU - Margolskee RF FAU - Nosrat, Christopher A AU - Nosrat CA LA - eng GR - R01 DC003055/DC/NIDCD NIH HHS/United States GR - R01 DC003155/DC/NIDCD NIH HHS/United States GR - R01 DC007628/DC/NIDCD NIH HHS/United States GR - R01-RDC007628/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120322 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (Neural Cell Adhesion Molecules) RN - 0 (Receptors, Purinergic P2X3) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Gene Expression MH - Gene Expression Regulation, Enzymologic/genetics MH - Membrane Glycoproteins/*biosynthesis/genetics MH - Mice MH - Mice, Transgenic MH - Neural Cell Adhesion Molecules/biosynthesis/genetics MH - Organ Size/genetics MH - Protein-Tyrosine Kinases/*biosynthesis/genetics MH - Receptors, Purinergic P2X3/biosynthesis/genetics MH - Taste Buds/*metabolism MH - Taste Perception MH - Tongue/*innervation/metabolism MH - Up-Regulation/genetics PMC - PMC3351349 EDAT- 2012/03/24 06:00 MHDA- 2012/07/14 06:00 PMCR- 2013/05/11 CRDT- 2012/03/24 06:00 PHST- 2012/03/24 06:00 [entrez] PHST- 2012/03/24 06:00 [pubmed] PHST- 2012/07/14 06:00 [medline] PHST- 2013/05/11 00:00 [pmc-release] AID - S0021-9258(20)60813-4 [pii] AID - M111.328476 [pii] AID - 10.1074/jbc.M111.328476 [doi] PST - ppublish SO - J Biol Chem. 2012 May 11;287(20):16791-800. doi: 10.1074/jbc.M111.328476. Epub 2012 Mar 22.