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

Nosrat, Irina V.; Margolskee, Robert F.; Nosrat, Christopher A.

doi:10.1074/jbc.m111.328476

Cited by 33 publications

(38 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Met66 allele impairs neuronal activity-dependent BDNF secretion 30 and thus may attenuate the rewarding effects of coffee and, in turn, motivation to consume coffee. The increasingly recognized roles of BDNF in the chemosensory system and conditioned taste preferences may also be relevant 31 . The index SNP (rs9902453) at 17q11.2 maps to the EFCAB5 gene and is in LD (CEU: r 2 >0.8) with SNPs that alter regulatory motifs for AhR 32 in the neighboring gene NSRP1 , but neither gene is an obvious candidate for coffee consumption.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Cornelis¹,

Byrne²,

Esko³

et al. 2014

Mol Psychiatry

255

235

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Cornelis¹,

Byrne²,

Esko³

et al. 2014

Mol Psychiatry

255

235

View full text Add to dashboard Cite

“…It is important to note however, that gustin genotypes predicted only a small percentage of the variance in papillae size, and shape, suggesting that other factors define these morphological characteristics. We did not investigate brain-derived neurotrophic factor (BDNF) which has also been implicated in papillae development and maintenance [73–75], and this also needs to be pursued in future investigations.…”

Section: Discussionmentioning

confidence: 99%

The Gustin (CA6) Gene Polymorphism, rs2274333 (A/G), as a Mechanistic Link between PROP Tasting and Fungiform Taste Papilla Density and Maintenance

et al. 2013

View full text Add to dashboard Cite

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.

show abstract

“…It is possible that the reduction in postnatal BDNF and innervation density in the taste bud may specifically reduce innervation to the PLCβ2 population of taste receptor cells because they lack BDNF. The overexpression of BDNF under the control of the α-gustducin promoter (which results in BDNF expression in half of the PLCβ2 population) also increases innervation to the taste bud (Nosrat et al, 2012). Therefore, the overexpression of BDNF in this location may also prevent the postnatal refinement of innervation within the taste bud.…”

Section: Discussionmentioning

confidence: 99%

Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation

Huang

Krimm

2015

Developmental Biology

View full text Add to dashboard Cite

The refinement of innervation is a common developmental mechanism that serves to increase the specificity of connections following initial innervation. In the peripheral gustatory system, the extent to which innervation is refined and how refinement might be regulated is unclear. The initial innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud innervation during postnatal development. An analysis of BDNF expression in BdnflacZ/+ mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing innervation. This reduction of innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development.

show abstract

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

Cited by 33 publications

References 59 publications

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

The Gustin (CA6) Gene Polymorphism, rs2274333 (A/G), as a Mechanistic Link between PROP Tasting and Fungiform Taste Papilla Density and Maintenance

Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation

Contact Info

Product

Resources

About