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Impaired sense of smell in a Drosophila Parkinson's model.

Poddighe S, Bhat KM, Setzu MD, Solla P, Angioy AM, Marotta R, Ruffilli R, Marrosu F, Liscia A - PLoS ONE (2013)

Bottom Line: The results obtained were compared with the same age-groups of wild type flies.We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles.Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

ABSTRACT
Parkinson's disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3-5 day-old flies, from 15-20 and from 27-30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments.

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Related in: MedlinePlus

Electroantennogram responses in wild type and PINK1B9 mutants.Dose-response relationships for olfactory stimulations in WT and PINK1B9 adult flies and their differences in signal amplitude. Histograms in A and D show the EAG results in flies from Group I (age range from 3 to 6 days), from Group II (age range from 15 to 20 days) in B and E and from Group III (age range from 27 to 30) in C and F. Values shown are mean ± S.E.M. of the EAG amplitude. Stimuli are dilutions of essential oils (rosemary, RM; lentisk, LT; myrtle, MT) and synthetic compounds (α-pinene, αp; hexanol, hex; isoamyl acetate, iso; ethyl 3-hydroxybutyrate, e3OH) administered in a 3-step dose from 0.1 to 10% in hexane. EAGs obtained in WT and PINK1B9 displayed strong similarities in the dose-response to stimuli; statistically significant differences were observed between WT and the mutant strains (* significantly different from its previous concentration; ** significantly different from its matching stimulus; P<0.05). In G, representative EAG tracings recorded in WT (upper) and PINK1B9 (lower) in response to olfactory stimulation with rosemary oil (RM) administered in increasing concentrations. The sample tracings show that the amplitude of the depolarization in the baseline is clearly higher in WT than in PINK1B9.
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pone-0073156-g002: Electroantennogram responses in wild type and PINK1B9 mutants.Dose-response relationships for olfactory stimulations in WT and PINK1B9 adult flies and their differences in signal amplitude. Histograms in A and D show the EAG results in flies from Group I (age range from 3 to 6 days), from Group II (age range from 15 to 20 days) in B and E and from Group III (age range from 27 to 30) in C and F. Values shown are mean ± S.E.M. of the EAG amplitude. Stimuli are dilutions of essential oils (rosemary, RM; lentisk, LT; myrtle, MT) and synthetic compounds (α-pinene, αp; hexanol, hex; isoamyl acetate, iso; ethyl 3-hydroxybutyrate, e3OH) administered in a 3-step dose from 0.1 to 10% in hexane. EAGs obtained in WT and PINK1B9 displayed strong similarities in the dose-response to stimuli; statistically significant differences were observed between WT and the mutant strains (* significantly different from its previous concentration; ** significantly different from its matching stimulus; P<0.05). In G, representative EAG tracings recorded in WT (upper) and PINK1B9 (lower) in response to olfactory stimulation with rosemary oil (RM) administered in increasing concentrations. The sample tracings show that the amplitude of the depolarization in the baseline is clearly higher in WT than in PINK1B9.

Mentions: We next sought to determine if PINK1B9 mutant adults exhibited reduced electrophysiological response in an odor-specific manner. We found that the olfactory stimulations consistently elicited a typical waveform EAG response with rapid depolarization followed by a slow recovery phase in both WT and in PINK1B9 mutant adults. The EAG values recorded in WT from e age group I were on the average higher than those obtained in mutant flies from the matching age group (P<0.05). Lower EAG values were measured when mutants were stimulated both with the oils and the synthetics. In detail the olfactory responses recorded from 15 specimens for both WT and PINK1B9 individuals in age group I exhibited a dose response in both strains for all the stimuli administered. Thus, all animals responded with a higher EAG amplitude when stimulated with increased concentrations of odors. The results are summarized in Figs. 2A and 2D. The EAG signal amplitudes evoked by stimuli were significantly lower in PINK1B9 than in WT for the majority of odors administered at the mid- and highest concentrations (P<0.05), with the exception of LT, which also displayed a significantly lower amplitude at the lowest concentration. Among the synthetic odors tested, the EAGs evoked by isoamyl acetate and ethyl 3-hydroxybutyrate in PINK1B9 did not result significantly lower than those detected in WT, even displaying an undersized amplitude. The only exception was for the stimulation with isoamyl acetate at the lowest concentration, where EAGs in PINK1B9 flies had a significantly lower amplitude than those in WT (P<0.05). Sample tracings of EAG recorded in WT and in PINK1B9 mutant adults in response to stimulation with RM essential oil at increasing concentrations are shown in Fig. 2G, where the signal amplitude in WT is clearly higher compared to mutants.


Impaired sense of smell in a Drosophila Parkinson's model.

Poddighe S, Bhat KM, Setzu MD, Solla P, Angioy AM, Marotta R, Ruffilli R, Marrosu F, Liscia A - PLoS ONE (2013)

Electroantennogram responses in wild type and PINK1B9 mutants.Dose-response relationships for olfactory stimulations in WT and PINK1B9 adult flies and their differences in signal amplitude. Histograms in A and D show the EAG results in flies from Group I (age range from 3 to 6 days), from Group II (age range from 15 to 20 days) in B and E and from Group III (age range from 27 to 30) in C and F. Values shown are mean ± S.E.M. of the EAG amplitude. Stimuli are dilutions of essential oils (rosemary, RM; lentisk, LT; myrtle, MT) and synthetic compounds (α-pinene, αp; hexanol, hex; isoamyl acetate, iso; ethyl 3-hydroxybutyrate, e3OH) administered in a 3-step dose from 0.1 to 10% in hexane. EAGs obtained in WT and PINK1B9 displayed strong similarities in the dose-response to stimuli; statistically significant differences were observed between WT and the mutant strains (* significantly different from its previous concentration; ** significantly different from its matching stimulus; P<0.05). In G, representative EAG tracings recorded in WT (upper) and PINK1B9 (lower) in response to olfactory stimulation with rosemary oil (RM) administered in increasing concentrations. The sample tracings show that the amplitude of the depolarization in the baseline is clearly higher in WT than in PINK1B9.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3757021&req=5

pone-0073156-g002: Electroantennogram responses in wild type and PINK1B9 mutants.Dose-response relationships for olfactory stimulations in WT and PINK1B9 adult flies and their differences in signal amplitude. Histograms in A and D show the EAG results in flies from Group I (age range from 3 to 6 days), from Group II (age range from 15 to 20 days) in B and E and from Group III (age range from 27 to 30) in C and F. Values shown are mean ± S.E.M. of the EAG amplitude. Stimuli are dilutions of essential oils (rosemary, RM; lentisk, LT; myrtle, MT) and synthetic compounds (α-pinene, αp; hexanol, hex; isoamyl acetate, iso; ethyl 3-hydroxybutyrate, e3OH) administered in a 3-step dose from 0.1 to 10% in hexane. EAGs obtained in WT and PINK1B9 displayed strong similarities in the dose-response to stimuli; statistically significant differences were observed between WT and the mutant strains (* significantly different from its previous concentration; ** significantly different from its matching stimulus; P<0.05). In G, representative EAG tracings recorded in WT (upper) and PINK1B9 (lower) in response to olfactory stimulation with rosemary oil (RM) administered in increasing concentrations. The sample tracings show that the amplitude of the depolarization in the baseline is clearly higher in WT than in PINK1B9.
Mentions: We next sought to determine if PINK1B9 mutant adults exhibited reduced electrophysiological response in an odor-specific manner. We found that the olfactory stimulations consistently elicited a typical waveform EAG response with rapid depolarization followed by a slow recovery phase in both WT and in PINK1B9 mutant adults. The EAG values recorded in WT from e age group I were on the average higher than those obtained in mutant flies from the matching age group (P<0.05). Lower EAG values were measured when mutants were stimulated both with the oils and the synthetics. In detail the olfactory responses recorded from 15 specimens for both WT and PINK1B9 individuals in age group I exhibited a dose response in both strains for all the stimuli administered. Thus, all animals responded with a higher EAG amplitude when stimulated with increased concentrations of odors. The results are summarized in Figs. 2A and 2D. The EAG signal amplitudes evoked by stimuli were significantly lower in PINK1B9 than in WT for the majority of odors administered at the mid- and highest concentrations (P<0.05), with the exception of LT, which also displayed a significantly lower amplitude at the lowest concentration. Among the synthetic odors tested, the EAGs evoked by isoamyl acetate and ethyl 3-hydroxybutyrate in PINK1B9 did not result significantly lower than those detected in WT, even displaying an undersized amplitude. The only exception was for the stimulation with isoamyl acetate at the lowest concentration, where EAGs in PINK1B9 flies had a significantly lower amplitude than those in WT (P<0.05). Sample tracings of EAG recorded in WT and in PINK1B9 mutant adults in response to stimulation with RM essential oil at increasing concentrations are shown in Fig. 2G, where the signal amplitude in WT is clearly higher compared to mutants.

Bottom Line: The results obtained were compared with the same age-groups of wild type flies.We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles.Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

ABSTRACT
Parkinson's disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3-5 day-old flies, from 15-20 and from 27-30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments.

Show MeSH
Related in: MedlinePlus