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CD36 is involved in oleic acid detection by the murine olfactory system.

Oberland S, Ackels T, Gaab S, Pelz T, Spehr J, Spehr M, Neuhaus EM - Front Cell Neurosci (2015)

Bottom Line: In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca(2+) imaging experiments is drastically reduced in young CD36 knock-out mice.Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period.Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology and Toxicology, University Hospital Jena, Friedrich-Schiller-University Jena Jena, Germany ; Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin Berlin, Germany ; Freie Universität-Berlin, Fachbereich Biologie, Chemie und Pharmazie Berlin, Germany.

ABSTRACT
Olfactory signals influence food intake in a variety of species. To maximize the chances of finding a source of calories, an animal's preference for fatty foods and triglycerides already becomes apparent during olfactory food search behavior. However, the molecular identity of both receptors and ligands mediating olfactory-dependent fatty acid recognition are, so far, undescribed. We here describe that a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and demonstrate a receptor-like localization of CD36 in olfactory cilia by STED microscopy. CD36-positive olfactory neurons share olfaction-specific transduction elements and project to numerous glomeruli in the ventral olfactory bulb. In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca(2+) imaging experiments is drastically reduced in young CD36 knock-out mice. Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period. Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system.

No MeSH data available.


Related in: MedlinePlus

Functional investigation of CD36 knockout mice. (A,B) Representative traces of local field potentials (electro-olfactogram, EOG) generated in the main olfactory epithelium of wild type (A) and CD36−/−(B) mice upon stimulation with a mixture of 100 odorants (Henkel 100). (C) Mean EOG responses to the odor mixture Henkel 100 from the main olfactory epithelium of wild type and CD36−/− mice showing no significant differences. CD36−/− mice possess normal ability to detect odorants. Data are shown as mean ± SEM of n = 6–8 mice at postnatal day 14 (3 individual recordings each). Significance was calculated using two sample t-test. Data are shown as mean ± SEM. (D,E) Representative traces (relative intensity vs. time) illustrating odor-, OA- and K+-dependent Ca2+ elevations in olfactory neurons from a wild type (black) and a CD36−/− mouse (red). Horizontal bars indicate stimulus application. OA concentrations as indicated. (F,G) Dose-dependent Ca2+ elevations recorded from fluo-4/AM loaded OSNs in acute tissue sections from wild type mice. (F) Overlay of average Ca2+ signals (gray curve; 11 randomly selected neurons) and an original trace from a single OSN (black) in response to increasing oleic acid (OA) concentrations (0.02, 0.2, and 20 μM). Relative fluorescence intensity is plotted as a function of time. Horizontal bars indicate duration of stimulus application. (G) Bar graph illustrating the relative proportion of OA-sensitive neurons as a function of stimulus concentration [n = 27 (2 nM); n = 11 (20 nM); n = 11 (200 nM)]. Data are shown as mean ± SEM. (H–J) Bar charts comparing different response characteristics as a function of genotype [wild type (black) vs. CD36−/− (gray)] and stimulus (odor-mix vs. OA). Signal parameters in response to odor (10 μM each) and OA (2 nM) are normalized to depolarization-dependent Ca2+ signals (K+; n = 11 randomly selected neurons). Maximum response amplitude [Ampmax (H)], rising speed [time-to-peak (I) and half-width; full duration at half maximum, FDHM (J)] are plotted. Asterisks denote statistical significance (unpaired, two-sided t-test; *p ≤ 0.05; **p ≤ 0.01; age P6–P9). Data are shown as mean ± SEM. (K) Bar diagram illustrating the portion of neurons responding to the odor-mix and to oleic acid, respectively, for wild type (black) and CD36−/− (gray) animals. Cell count was normalized to K+-sensitive neurons in each experiment [wild type: n = 40 (odor-mix), 27 (OA, 2 nM), 37 (OA, 20 μM); CD36−/−: n = 26 (odor-mix), 40 (OA, 2 nM and 20 μM)]. Similar portions of neurons responded to the odor mix. By contrast, the number of OA sensing neurons was significantly reduced in CD36−/− mice. Significance was calculated using unpaired, two-sided t-tests (**p ≤ 0.01; ***p < 0.005; age P6–P9). Data are shown as mean ± SEM.
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Figure 9: Functional investigation of CD36 knockout mice. (A,B) Representative traces of local field potentials (electro-olfactogram, EOG) generated in the main olfactory epithelium of wild type (A) and CD36−/−(B) mice upon stimulation with a mixture of 100 odorants (Henkel 100). (C) Mean EOG responses to the odor mixture Henkel 100 from the main olfactory epithelium of wild type and CD36−/− mice showing no significant differences. CD36−/− mice possess normal ability to detect odorants. Data are shown as mean ± SEM of n = 6–8 mice at postnatal day 14 (3 individual recordings each). Significance was calculated using two sample t-test. Data are shown as mean ± SEM. (D,E) Representative traces (relative intensity vs. time) illustrating odor-, OA- and K+-dependent Ca2+ elevations in olfactory neurons from a wild type (black) and a CD36−/− mouse (red). Horizontal bars indicate stimulus application. OA concentrations as indicated. (F,G) Dose-dependent Ca2+ elevations recorded from fluo-4/AM loaded OSNs in acute tissue sections from wild type mice. (F) Overlay of average Ca2+ signals (gray curve; 11 randomly selected neurons) and an original trace from a single OSN (black) in response to increasing oleic acid (OA) concentrations (0.02, 0.2, and 20 μM). Relative fluorescence intensity is plotted as a function of time. Horizontal bars indicate duration of stimulus application. (G) Bar graph illustrating the relative proportion of OA-sensitive neurons as a function of stimulus concentration [n = 27 (2 nM); n = 11 (20 nM); n = 11 (200 nM)]. Data are shown as mean ± SEM. (H–J) Bar charts comparing different response characteristics as a function of genotype [wild type (black) vs. CD36−/− (gray)] and stimulus (odor-mix vs. OA). Signal parameters in response to odor (10 μM each) and OA (2 nM) are normalized to depolarization-dependent Ca2+ signals (K+; n = 11 randomly selected neurons). Maximum response amplitude [Ampmax (H)], rising speed [time-to-peak (I) and half-width; full duration at half maximum, FDHM (J)] are plotted. Asterisks denote statistical significance (unpaired, two-sided t-test; *p ≤ 0.05; **p ≤ 0.01; age P6–P9). Data are shown as mean ± SEM. (K) Bar diagram illustrating the portion of neurons responding to the odor-mix and to oleic acid, respectively, for wild type (black) and CD36−/− (gray) animals. Cell count was normalized to K+-sensitive neurons in each experiment [wild type: n = 40 (odor-mix), 27 (OA, 2 nM), 37 (OA, 20 μM); CD36−/−: n = 26 (odor-mix), 40 (OA, 2 nM and 20 μM)]. Similar portions of neurons responded to the odor mix. By contrast, the number of OA sensing neurons was significantly reduced in CD36−/− mice. Significance was calculated using unpaired, two-sided t-tests (**p ≤ 0.01; ***p < 0.005; age P6–P9). Data are shown as mean ± SEM.

Mentions: The olfactory function in wild type and CD36−/− mice was first analyzed by recording epithelial field potentials (electro-olfactogram, EOG), elicited by a complex odorant mixture. The signals were indistinguishable between wild type and CD36−/− mice (Figures 9A–C), indicating that CD36−/− mice are not generally anosmic.


CD36 is involved in oleic acid detection by the murine olfactory system.

Oberland S, Ackels T, Gaab S, Pelz T, Spehr J, Spehr M, Neuhaus EM - Front Cell Neurosci (2015)

Functional investigation of CD36 knockout mice. (A,B) Representative traces of local field potentials (electro-olfactogram, EOG) generated in the main olfactory epithelium of wild type (A) and CD36−/−(B) mice upon stimulation with a mixture of 100 odorants (Henkel 100). (C) Mean EOG responses to the odor mixture Henkel 100 from the main olfactory epithelium of wild type and CD36−/− mice showing no significant differences. CD36−/− mice possess normal ability to detect odorants. Data are shown as mean ± SEM of n = 6–8 mice at postnatal day 14 (3 individual recordings each). Significance was calculated using two sample t-test. Data are shown as mean ± SEM. (D,E) Representative traces (relative intensity vs. time) illustrating odor-, OA- and K+-dependent Ca2+ elevations in olfactory neurons from a wild type (black) and a CD36−/− mouse (red). Horizontal bars indicate stimulus application. OA concentrations as indicated. (F,G) Dose-dependent Ca2+ elevations recorded from fluo-4/AM loaded OSNs in acute tissue sections from wild type mice. (F) Overlay of average Ca2+ signals (gray curve; 11 randomly selected neurons) and an original trace from a single OSN (black) in response to increasing oleic acid (OA) concentrations (0.02, 0.2, and 20 μM). Relative fluorescence intensity is plotted as a function of time. Horizontal bars indicate duration of stimulus application. (G) Bar graph illustrating the relative proportion of OA-sensitive neurons as a function of stimulus concentration [n = 27 (2 nM); n = 11 (20 nM); n = 11 (200 nM)]. Data are shown as mean ± SEM. (H–J) Bar charts comparing different response characteristics as a function of genotype [wild type (black) vs. CD36−/− (gray)] and stimulus (odor-mix vs. OA). Signal parameters in response to odor (10 μM each) and OA (2 nM) are normalized to depolarization-dependent Ca2+ signals (K+; n = 11 randomly selected neurons). Maximum response amplitude [Ampmax (H)], rising speed [time-to-peak (I) and half-width; full duration at half maximum, FDHM (J)] are plotted. Asterisks denote statistical significance (unpaired, two-sided t-test; *p ≤ 0.05; **p ≤ 0.01; age P6–P9). Data are shown as mean ± SEM. (K) Bar diagram illustrating the portion of neurons responding to the odor-mix and to oleic acid, respectively, for wild type (black) and CD36−/− (gray) animals. Cell count was normalized to K+-sensitive neurons in each experiment [wild type: n = 40 (odor-mix), 27 (OA, 2 nM), 37 (OA, 20 μM); CD36−/−: n = 26 (odor-mix), 40 (OA, 2 nM and 20 μM)]. Similar portions of neurons responded to the odor mix. By contrast, the number of OA sensing neurons was significantly reduced in CD36−/− mice. Significance was calculated using unpaired, two-sided t-tests (**p ≤ 0.01; ***p < 0.005; age P6–P9). Data are shown as mean ± SEM.
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Figure 9: Functional investigation of CD36 knockout mice. (A,B) Representative traces of local field potentials (electro-olfactogram, EOG) generated in the main olfactory epithelium of wild type (A) and CD36−/−(B) mice upon stimulation with a mixture of 100 odorants (Henkel 100). (C) Mean EOG responses to the odor mixture Henkel 100 from the main olfactory epithelium of wild type and CD36−/− mice showing no significant differences. CD36−/− mice possess normal ability to detect odorants. Data are shown as mean ± SEM of n = 6–8 mice at postnatal day 14 (3 individual recordings each). Significance was calculated using two sample t-test. Data are shown as mean ± SEM. (D,E) Representative traces (relative intensity vs. time) illustrating odor-, OA- and K+-dependent Ca2+ elevations in olfactory neurons from a wild type (black) and a CD36−/− mouse (red). Horizontal bars indicate stimulus application. OA concentrations as indicated. (F,G) Dose-dependent Ca2+ elevations recorded from fluo-4/AM loaded OSNs in acute tissue sections from wild type mice. (F) Overlay of average Ca2+ signals (gray curve; 11 randomly selected neurons) and an original trace from a single OSN (black) in response to increasing oleic acid (OA) concentrations (0.02, 0.2, and 20 μM). Relative fluorescence intensity is plotted as a function of time. Horizontal bars indicate duration of stimulus application. (G) Bar graph illustrating the relative proportion of OA-sensitive neurons as a function of stimulus concentration [n = 27 (2 nM); n = 11 (20 nM); n = 11 (200 nM)]. Data are shown as mean ± SEM. (H–J) Bar charts comparing different response characteristics as a function of genotype [wild type (black) vs. CD36−/− (gray)] and stimulus (odor-mix vs. OA). Signal parameters in response to odor (10 μM each) and OA (2 nM) are normalized to depolarization-dependent Ca2+ signals (K+; n = 11 randomly selected neurons). Maximum response amplitude [Ampmax (H)], rising speed [time-to-peak (I) and half-width; full duration at half maximum, FDHM (J)] are plotted. Asterisks denote statistical significance (unpaired, two-sided t-test; *p ≤ 0.05; **p ≤ 0.01; age P6–P9). Data are shown as mean ± SEM. (K) Bar diagram illustrating the portion of neurons responding to the odor-mix and to oleic acid, respectively, for wild type (black) and CD36−/− (gray) animals. Cell count was normalized to K+-sensitive neurons in each experiment [wild type: n = 40 (odor-mix), 27 (OA, 2 nM), 37 (OA, 20 μM); CD36−/−: n = 26 (odor-mix), 40 (OA, 2 nM and 20 μM)]. Similar portions of neurons responded to the odor mix. By contrast, the number of OA sensing neurons was significantly reduced in CD36−/− mice. Significance was calculated using unpaired, two-sided t-tests (**p ≤ 0.01; ***p < 0.005; age P6–P9). Data are shown as mean ± SEM.
Mentions: The olfactory function in wild type and CD36−/− mice was first analyzed by recording epithelial field potentials (electro-olfactogram, EOG), elicited by a complex odorant mixture. The signals were indistinguishable between wild type and CD36−/− mice (Figures 9A–C), indicating that CD36−/− mice are not generally anosmic.

Bottom Line: In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca(2+) imaging experiments is drastically reduced in young CD36 knock-out mice.Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period.Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology and Toxicology, University Hospital Jena, Friedrich-Schiller-University Jena Jena, Germany ; Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin Berlin, Germany ; Freie Universität-Berlin, Fachbereich Biologie, Chemie und Pharmazie Berlin, Germany.

ABSTRACT
Olfactory signals influence food intake in a variety of species. To maximize the chances of finding a source of calories, an animal's preference for fatty foods and triglycerides already becomes apparent during olfactory food search behavior. However, the molecular identity of both receptors and ligands mediating olfactory-dependent fatty acid recognition are, so far, undescribed. We here describe that a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and demonstrate a receptor-like localization of CD36 in olfactory cilia by STED microscopy. CD36-positive olfactory neurons share olfaction-specific transduction elements and project to numerous glomeruli in the ventral olfactory bulb. In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca(2+) imaging experiments is drastically reduced in young CD36 knock-out mice. Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period. Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system.

No MeSH data available.


Related in: MedlinePlus