Behavioral Phenotyping and Pathological Indicators of Parkinson's Disease in C. elegans Models

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder with symptoms that progressively worsen with age. Pathologically, PD is characterized by the aggregation of α-synuclein in cells of the substantia nigra in the brain and loss of dopaminergic neurons. This pathology is associated with impaired movement and reduced cognitive function. The etiology of PD can be attributed to a combination of environmental and genetic factors. A popular animal model, the nematode roundworm Caenorhabditis elegans, has been frequently used to study the role of genetic and environmental factors in the molecular pathology and behavioral phenotypes associated with PD. The current review summarizes cellular markers and behavioral phenotypes in transgenic and toxin-induced PD models of C. elegans.

Keywords: Caenorhabditis elegans (C. elegans); Parkinson's disease (PD); behavioral phenotyping; dopamine; pathological markers.

Figure 1

Representative image of the head region of a day-7 adult of strain NL5901 ([unc-54p::α-synuclein::YFP+unc-119]), maintained at 22°C, showing α-synuclein protein expression in the body wall muscle cells. The white arrow indicates one of multiple visible protein aggregates. Scale bar, 50 μm; magnification, 50×. (Original image taken by the authors for this paper on a Zeiss LSM 510 laser scanning confocal microscope).

Figure 2

Representative images of the head regions of day-5 adults of strain BZ555 ([dat-1p::GFP]), maintained at 22°C. The images show (a) six healthy dopaminergic neurons (four CEPs [white arrows] and two ADEs [yellow arrows]), (b) two intact cell processes or dendrites (white arrows) of the four CEP neurons, which extend from the pharynx to the tip of the nose (c) the shrinkage of a cell body (white arrow), (d) neuritic blebbing (white arrows), and (e) abrupt gaps or breaks in the dendrites or cell processes (white arrows) caused by 50 mM 6-OHDA. (Scale bars, 50 μm; magnification, 50×. Original image taken by the authors for this paper on a Zeiss LSM 510 laser scanning confocal microscope).

Figure 3

Representative images of Nile red staining of lipid content in live, day-5 adult C. elegans in (a) a wild-type N2 animal under fluorescence microscopy and (b) an OW13 [unc-54p::α-synuclein::YFP + unc-119(+)] animal under fluorescence microscopy. Image (c) depicts an overlay of phase contrast and fluorescence microscopy of a wild-type N2 animal and (d) shows an overlay of phase contrast and fluorescence microscopy of an OW13 animal. Strains were maintained at 22°C. White arrows represent stained fat droplets. Scale bar, 50 μm; magnification, 60x. Original image taken by the authors for this paper on an Olympus FLUORVIEW FV10i confocal microscope.