Impaired sense of smell in a Drosophila Parkinson's model.
Impaired sense of smell in a Drosophila Parkinson's model.
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DOI：
10.1371/journal.pone.0073156
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liscia A
中科院分区：
文献类型：
--
作者：
Poddighe S;Bhat KM;Setzu MD;Solla P;Angioy AM;Marotta R;Ruffilli R;Marrosu F;Liscia A
帕金森病（Parkinson's disease，PD）是最常见的神经退行性疾病之一，其临床特征为震颤、运动不能和强直。一些研究表明，PD患者在疾病的最早发作时表现出嗅觉障碍。果蝇Drosophila melanogaster正在成为研究神经退行性疾病的一种强有力的模式生物。我们试图使用这个系统来探索嗅觉功能障碍，如果有的话，在PINK 1突变体，这是一个模型的PD。PINK 1突变体显示出许多重要的疾病诊断症状，如运动不能运动行为。在本研究中，据我们所知，我们首次描述了有关PINK 1突变果蝇嗅觉功能的神经生理学和神经解剖学结果。在PINK 1突变成虫的生命周期中的三个不同时间点记录了对合成和天然挥发物（精油）的反应的触角电位：一个来自3-5天大的苍蝇，从15-20天和27-30天。将所得结果与相同年龄组的野生型苍蝇进行比较。我们发现突变体成虫对1-己醇、α-蒎烯和精油挥发物的嗅觉反应降低。随着果蝇年龄的增长，突变成虫的嗅觉反应下降得更多。在这些突变体的触角叶的免疫组织学分析显示结构异常，特别是在表达的Bruchpilot蛋白，突触活性区的标记。电生理和形态学结果的结合表明，改变突触组织可能是由于神经退行性过程。我们的研究结果表明，该模型可以作为一种工具，了解PD的发病机制和病理生理。这些结果有助于探索使用嗅觉作为监测PD进展和开发新治疗方法的潜力。
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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影响因子：
4.5
作者：
Imai Y;Kanao T;Sawada T;Kobayashi Y;Moriwaki Y;Ishida Y;Takeda K;Ichijo H;Lu B;Takahashi R
通讯作者：
Takahashi R
DOI：
10.1073/pnas.0605321104
发表时间：
2007-03-27
影响因子：
11.1
作者：
Keller, Andreas;Vosshall, Leslie B.
通讯作者：
Vosshall, Leslie B.
影响因子：
9.3
作者：
Latourelle, Jeanne C.;Sun, Mei;Lew, Mark F.;Suchowersky, Oksana;Klein, Christine;Golbe, Lawrence I.;Mark, Margery H.;Growdon, John H.;Wooten, G. Frederick;Watts, Ray L.;Guttman, Mark;Racette, Brad A.;Perlmutter, Joel S.;Ahmed, Anwar;Shill, Holly A.;Singer, Carlos;Goldwurm, Stefano;Pezzoli, Gianni;Zini, Michela;Saint-Hilaire, Marie H.;Hendricks, Audrey E.;Williamson, Sally;Nagle, Michael W.;Wilk, Jemma B.;Massood, Tiffany;Huskey, Karen W.;Laramie, Jason M.;DeStefano, Anita L.;Baker, Kenneth B.;Itin, Ilia;Litvan, Irene;Nicholson, Garth;Corbett, Alastair;Nance, Martha;Drasby, Edward;Isaacson, Stuart;Burn, David J.;Chinnery, Patrick F.;Pramstaller, Peter P.;Al-hinti, Jomana;Moller, Anette T.;Ostergaard, Karen;Sherman, Scott J.;Roxburgh, Richard;Snow, Barry;Slevin, John T.;Cambi, Franca;Gusella, James F.;Myers, Richard H.
通讯作者：
Myers, Richard H.
影响因子：
9.2
作者：
Dekker, T;Ibba, I;Hansson, BS
通讯作者：
Hansson, BS
影响因子：
--
作者：
Ibba, Irene;Angioy, Anna Maria;Dekker, Teun
通讯作者：
Dekker, Teun