BDNF is required for the normal development of taste neurons in vivo

Zhang, Chunxiao; Brandemihl, Adam; Lau, David H.; Lawton, Anne; Oakley, Bruce

doi:10.1097/00001756-199703030-00039

Cited by 87 publications

(86 citation statements)

References 12 publications

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“…BDNF -/-mice exhibit a loss of gustatory innervation and a subsequent loss of taste buds and gustatory papillae (Nosrat et al, 1997;Zhang et al, 1997). Interestingly, similar deficits were seen in BDNF NT3/NT3 mice with a distinct disruption of gustatory innervation while lingual somatosensory innervation appeared intact (Fig.…”

Section: The Nt3/nt3 Alleles Supports Neither Survival Of Taste Neuromentioning

confidence: 81%

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BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development

et al. 2003

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Neurotrophins have multiple functions during peripheral nervous system development such as controlling neuronal survival, target innervation and synaptogenesis. Neurotrophin specificity has been attributed to the selective expression of the Trk tyrosine kinase receptors in different neuronal subpopulations. However, despite overlapping expression of TrkB and TrkC in many sensory ganglia, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) null mutant mice display selective losses in neuronal subpopulations. In the present study we have replaced the coding part of theBDNF gene in mice with that of NT3 (BDNFNT3/NT3)to analyse the specificity and selective roles of BDNF and NT3 during development. Analysis of BDNFNT3/NT3 mice showed striking differences in the ability of NT3 to promote survival, short-range innervation and synaptogenesis in different sensory systems. In the cochlea, specificity is achieved by a tightly controlled spatial and temporal ligand expression. In the vestibular system TrkB or TrkC activation is sufficient to promote vestibular ganglion neuron survival, while TrkB activation is required to promote proper innervation and synaptogenesis. In the gustatory system, NT3 is unable to replace the actions of BDNF possibly because of a temporally selective expression of TrkB in taste neurons. We conclude that there is no general mechanism by which neurotrophin specificity is attained and that specificity is achieved by (i) a tightly controlled spatial and temporal expression of ligands, (ii) different Trk receptors playing distinct roles within the same neuronal subpopulation, or (iii) selective receptor expression in sensory neuron subpopulations.

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Section: The Nt3/nt3 Alleles Supports Neither Survival Of Taste Neuromentioning

confidence: 81%

“…BDNF -/-mice display a specific set of deficits in their peripheral gustatory system, including general loss of taste buds, innervation deficits in the remaining taste buds, and fewer and malformed tongue papillae. Instead, NT3 -/-animals lose their lingual somatosensory innervation (Nosrat et al, 1997;Zhang et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development

et al. 2003

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“…It has been shown that BDNF is required for gustatory development 43,44 and that TrkB is expressed in the olfactory bulb 45 . Since the moderate-fat diet is more palatable, these observations raise the possibility that developmental defects and/or malfunction of the gustatory or olfactory system may affect feeding behavior of the trkB mutant on the moderatefat diet.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor

et al. 2003

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The melanocortin-4 receptor (MC4R) is critically involved in regulating energy balance, and obesity has been observed in mice with mutations in the gene for brain-derived neurotrophic factor (BDNF). Here we report that BDNF is expressed at high levels in the ventromedial hypothalamus (VMH) where its expression is regulated by nutritional state and by MC4R signaling. In addition, similar to MC4R mutants, mouse mutants that expresses the BDNF receptor TrkB at a quarter of the normal amount showed hyperphagia and excessive weight gain on higher-fat diets. Furthermore, BDNF infusion into the brain suppressed the hyperphagia and excessive weight gain observed on higherfat diets in mice with deficient MC4R signaling. These results show that MC4R signaling controls BDNF expression in the VMH and support the hypothesis that BDNF is an important effector through which MC4R signaling controls energy balance.Neurotrophins are a family of structurally related growth factors, including brain-derived neurotrophic factor (BDNF), that exert many of their effects on neurons through Trk receptor tyrosine kinases. Among these, BDNF and its receptor TrkB are the most widely and abundantly expressed in the brain. BDNF has been shown to regulate neuronal development and to modulate synaptic plasticity 1 . Obesity phenotypes have been observed in BDNF heterozygous mice and in mice in which the BDNF gene has been deleted in excitatory neurons in the brain 2-4 . These mutants also show hyperactivity, hyperleptinaemia, hyperinsulinaemia, hyperglycemia and increased linear growth 3,4 . Moreover, both central and peripheral administration of BDNF decrease food intake, increase energy expenditure and ameliorate hyperinsulinaemia and hyperglycemia in diabetic db/db mice 5-8 . However, the means by which BDNF alters energy balance and the relationship of TrkB signaling to the major pathways previously shown to be involved in the regulation of energy balance remain unknown. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. The status of energy balance is communicated to the hypothalamus through neuronal and hormonal signals. Several hypothalamic nuclei are involved in the regulation of energy balance, including the ventromedial (VMH), paraventricular (PVN) and arcuate (ARC) hypothalamic nuclei and the lateral hypothalamic area (LH). Although the observation that bilateral VMH lesions produce hyperphagia and obesity has implicated this region in the regulation of energy balance 9-11 , the neural mechanisms through which the VMH functions to influence energy balance are not clear. NIH Public AccessOne of the major signals that serves as a monitor of energy balance is leptin, a polypeptide generated in adipocytes 12 . One of the main targets of leptin in the hypothalamus is the ARC, a region containing at least two distinct populations of neurons 13-15 . One population of neurons expresses two orexigenic polypeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), whereas the other...

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“…Sensory innervation of the fungiform and cir-cumvallate papillae is also reduced in mice lacking BDNF (BDNF À/À ). Consequently, fungiform and circumvallate taste buds are lost in BDNF null mice (Nosrat et al, 1997;Zhang et al, 1997;Cooper and Oakley, 1998;Mistretta et al, 1999). Fungiform papillae are also lost in NT4 À/À mice, but circumvallate papilla are normal (Liebl et al, 1999).…”

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confidence: 99%

Mice lacking the p75 receptor fail to acquire a normal complement of taste buds and geniculate ganglion neurons by adulthood

Krimm

2006

Anat. Rec.

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Brain-derived neurotrophic factor and neurotrophin-4 are required for normal taste bud development. Although these neurotrophins normally function via the tyrosine kinase receptor, trkB, they also bind to the panneurotrophin receptor, p75. The goal of the present study was to determine whether the p75 receptor is required for the development or maintenance of a full complement of adult taste buds. Mice with p75 null mutations lose 34% of their circumvallate taste buds, 36% of their fungiform papillae, and 26% of their fungiform taste buds by adulthood. The reduction of taste buds in the adult circumvallate papilla was similar to that observed previously at postnatal day 7 (Fan et al. Brain Res Dev Brain Res 2004;150:23-39). Taken together, these findings indicate that the p75 receptor is critical for the development of a full complement of taste buds, but is not required for maintenance of circumvallate taste buds in adulthood. Immunolabeling for p75 was not observed in taste buds, indicating that p75 signaling influences taste bud number indirectly. Geniculate ganglion neurons, which provides innervation to fungiform taste buds, express the p75 receptor. Mice with p75 null mutations also have fewer neurons in the geniculate ganglion. Together, these results suggest that the p75 receptor is important for the survival of geniculate neurons and geniculate neuron survival is required for the development of a full complement of taste buds by adulthood.

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BDNF is required for the normal development of taste neurons in vivo

Cited by 87 publications

References 12 publications

BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development

BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development

Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor

Mice lacking the p75 receptor fail to acquire a normal complement of taste buds and geniculate ganglion neurons by adulthood

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