Sensation of smell does not determine nutritional status in patients with cystic fibrosis

Aitken, Moira L.; Martinez, Steve R.; McDonald, Gwendolyn J.; Seifert, Catherine C.; Burke, Wylie

doi:10.1002/(sici)1099-0496(199707)24:1<52::aid-ppul9>3.0.co;2-l

Cited by 10 publications

(14 citation statements)

References 21 publications

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“…Interestingly, there are studies reporting a decrease in olfactory function in human CF patients (1,18,19,32,39). One study reported 55% of the CF patients studied (mean age 28 yr) had a decreased sensitivity of smell (1). This study found (as was the case with our CF mice) that the decreased sensitivity of smell in the CF patients (age 14 -53 yr, mean age 28 Ϯ 8 yr) was negatively correlated with age of the patients (P Յ 0.01).…”

Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

“…In human CF patients, it has not previously been suggested that the decrease in olfactory function may be related to a defect in the OE. Rather, it has been suggested that sinus infection or obstruction may be a likely cause of the CF-related partial anosmia (1,32). [There is one early study in which CF children were reported to have an enhanced sense of smell compared with normal controls (17).…”

Section: Discussionmentioning

confidence: 99%

“…[There is one early study in which CF children were reported to have an enhanced sense of smell compared with normal controls (17). However, virtually every subsequent study has refuted this finding (1,18,19,39)].…”

Section: Discussionmentioning

confidence: 99%

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Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

Grubb¹,

Rogers²,

Kulaga

et al. 2007

American Journal of Physiology-Cell Physiology

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In normal nasal epithelium, the olfactory receptor neurons (ORNs) are continuously replaced through the differentiation of progenitor cells. The olfactory epithelium (OE) of the cystic fibrosis (CF) mouse appears normal at birth, yet by 6 mo of age, a marked dysmorphology of sustentacular cells and a dramatic reduction in olfactory receptor neurons are evident. Electroolfactograms revealed that the odor-evoked response in 30-day-old CF mice was reduced approximately 45%; in older CF mice, a approximately 70% reduction was observed compared with the wild type (WT) response. Consistent with studies of CF airway epithelia, Ussing chamber studies of OE isolated from CF mice showed a lack of forskolin-stimulated Cl(-) secretion and an approximately 12-fold increase in amiloride-sensitive sodium absorption compared with WT mice. We hypothesize that the marked hyperabsorption of Na(+), most likely by olfactory sustentacular cells, leads to desiccation of the surface layer in which the sensory cilia reside, followed by degeneration of the ORNs. The CF mouse thus provides a novel model to examine the mechanisms of disease-associated loss of olfactory function.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

Grubb¹,

Rogers²,

Kulaga

et al. 2007

American Journal of Physiology-Cell Physiology

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“…CF‐associated olfactory deficits have been reported (Aitken et al, ; Henriksson et al, ; Lindig et al, ), affecting odor thresholds but not odor identification, which suggests dysfunction of the olfactory epithelium (OE) itself (Lindig et al, ). Experimentally, the OE of CFTR‐null mice serves as a CF model system because it shares similar electrophysiological and ion transport profiles with the human CF airways (Grubb et al, ,b, ; Delaney et al, ).…”

mentioning

confidence: 99%

Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal homeostasis

Pfister

Weber

Härtig

et al. 2014

J of Comparative Neurology

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The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion transport deficiencies reported in human CF airways, as well as progressive neuronal loss, suggesting defects in olfactory neuron homeostasis. Microvillar cells, a specialized OE cell-subtype, have been implicated in maintaining tissue homeostasis. These cells are endowed with a PLCβ2/IP3 R3/TRPC6 signal transduction pathway modulating release of neuropeptide Y (NPY), which stimulates OE stem cell activity. It is unknown, however, whether microvillar cells also mediate the deficits observed in CFTR-null mice. Here we show that Cftr mRNA in mouse OE is exclusively localized in microvillar cells and CFTR immunofluorescence is coassociated with the scaffolding protein NHERF-1 and PLCβ2 in microvilli. In CFTR-null mice, PLCβ2 was undetectable, NHERF-1 mislocalized, and IP3 R3 more intensely stained, along with increased levels of NPY, suggesting profound alteration of the PLCβ2/IP3 R3 signaling pathway. In addition, basal olfactory neuron homeostasis was altered, shown by increased progenitor cell proliferation, differentiation, and apoptosis and by reduced regenerative capacity following methimazole-induced neurodegeneration. The importance of CFTR in microvillar cells was further underscored by decreased thickness of the OE mucus layer and increased numbers of immune cells within this tissue in CFTR-KO mice. Finally, we observed enhanced immune responses to an acute viral-like infection, as well as hyper-responsiveness to chemical and physical stimuli applied intranasally. Taken together, these data strengthen the notion that microvillar cells in the OE play a key role in maintaining tissue homeostasis and identify several mechanisms underlying this regulation through the multiple functions of CFTR.

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Clinical Disorders of Olfaction

Doty

2015

Handbook of Olfaction and Gustation

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Sensation of smell does not determine nutritional status in patients with cystic fibrosis

Cited by 10 publications

References 21 publications

Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal homeostasis

Clinical Disorders of Olfaction

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