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Review
. 2022 Dec;16(1):275-298.
doi: 10.1080/19336934.2022.2087484.

Studies of neurodegenerative diseases using Drosophila and the development of novel approaches for their analysis

Yohei Nitta  1 , Atsushi Sugie  1
Affiliations
Review

Studies of neurodegenerative diseases using Drosophila and the development of novel approaches for their analysis

Yohei Nitta et al. Fly (Austin). 2022 Dec.

Abstract

The use of Drosophila in neurodegenerative disease research has contributed to the identification of modifier genes for the pathology. The basis for neurodegenerative disease occurrence in Drosophila is the conservation of genes across species and the ability to perform rapid genetic analysis using a compact brain. Genetic findings previously discovered in Drosophila can reveal molecular pathologies involved in human neurological diseases in later years. Disease models using Drosophila began to be generated during the development of genetic engineering. In recent years, results of reverse translational research using Drosophila have been reported. In this review, we discuss research on neurodegenerative diseases; moreover, we introduce various methods for quantifying neurodegeneration in Drosophila.

Keywords: Drosophila; neurodegenerative diseases; reverse translational research.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Reverse translational research using Drosophila.
Figure 2.
Figure 2.
Traditional methods for evaluating neurodegeneration using Drosophila. (A) The dorsal view of the head of Drosophila and a cross-sectional view of the visual system. 700–800 ommatidia are aligned in the retina. Each ommatidium has 8 types of photoreceptors: R1-6 project their axons to the first optic ganglion lamina, and R7-8 project their axons to the second optic ganglion medulla to transmit light information to the brain. (B-D) Structural defects observed in Drosophila compound eye (B), pseudopupil loss (C), and the retinal thickness and vacuolization (D) provide simple methods for evaluating the cytotoxicity of disease-associated proteins. (E) Life span analysis. The Kaplan-Meier survival curve is used to compare the lifespan of different groups.
Figure 3.
Figure 3.
Evaluation methods of neural function using Drosophila. (A) Climbing assay. It is a measurement of motor function taking advantage of the fly’s negative geotaxis. (B) Olfactory memory assay using T-maze. At the training phase, unconditioned stimulus (US) such as electric shock and sweetness such as sucrose is associated with the odour in the training tube. Next, another odour is presented, without US. In the test phase, the two odours used in the training are presented to the trained fly from both ends of the test tube, and the performance index is quantified by which odour attracted the fly. In the figure, the associative learning between odour A and electric shock, called aversive learning, leads to the learning flies avoiding odour A. (C) Schematic diagrams of Actogram. Actogram is a double-plotted graphical representation of the phases of an organism’s daily activity and resting time. Grey shading indicates the dark phase. In controls, the level of activity increases in the morning and evening, but when the circadian rhythm is disrupted by the expression of disease gene, this time-specific increase is not observed. (D) Schematic diagrams of ERG trace. In healthy flies (left panel), the ERG traces are derived from photoreceptor activity (depolarisation and repolarisation, white arrow heads in the figure) and from postsynaptic neuron activity (on-transient and off-transient, black arrow heads in the figure). When the pathological gene is expressed, the ERG trace can be used to estimate what part of the visual system is impaired.
Figure 4.
Figure 4.
Cell types and experimental systems of Drosophila for evaluating the effects of disease protein toxicity on each region in neurone. (A) the number of cell bodies is quantified by visualisation of the dopaminergic or the cholinergic neurones. (B) The degeneration of neurites is evaluated in dendrite (dendritic arborisation neurone) and axons (wing nerve, leg motor neurone, photoreceptor neurone, and olfactory receptor neurone). (C) The number and the structure of synapse is quantified in neuromuscular junction, photoreceptor axon, and olfactory receptor neurone.
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Publication types

Grants and funding

This work was supported by the Japan Agency for Medical Research and Development (AMED) [JP22ek019484s]; The Ministry of Education, Culture, Sports, Science and Technology of Japan [#19K22592 and #21H02837]; GSK Japan Research Grant 2022 [AS2021A000166849]; The Ministry of Education, Culture, Sports, Science and Technology of Japan [#18K14835, #18J00367 and #21K15619].

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