Abstract
Drosophila models of Parkinson's disease are characterized by two principal phenotypes: the specific loss of dopaminergic (DA) neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analyzed the DA system and motor behavior in aging Drosophila. DA neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH > mCD8::GFP and cell type-specific MARCM clones revealed that DA neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, DA neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity, and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH > Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct DA behaviors in Drosophila. Moreover, DA neurons were maintained between early- and late life, as quantified by TH > mCD8::GFP and anti-TH labeling, indicating that adult onset, age-related degeneration of DA neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson's disease as well as other disorders affecting DA neurons and movement control.
Highlights
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra of the ventral midbrain, neuropathology is not limited to this region (Braak and Del Tredici, 2008)
We focussed on six major clusters in the central brain that can be annotated according to their anatomical position (Figures 1B,D): paired posterior lateral 1 and 2 (PPL1 and PPL2); paired posterior medial 1 and 2 (PPM1/2) which are often grouped together because of their close proximity; paired posterior medial 3 (PPM3); paired anterior lateral (PAL), and paired anterior medial (PAM)
Drosophila models of PD are characterized by two principal phenotypes related to parkinsonism: the specific loss of subsets of DA neurons in the aging brain and locomotion defects (Hirth, 2010)
Summary
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra of the ventral midbrain, neuropathology is not limited to this region (Braak and Del Tredici, 2008). Loss of DA innervation of the putamen gives rise to the characteristic locomotor abnormalities associated with the disease, including slowness or absence of movement (bradykinesia and akinesia respectively), muscular rigidity, unstable posture, and resting tremor (Lees et al, 2009). Males appear to be 1.5 times more likely to develop PD than females, it is not currently known why this is the case (Lees et al, 2009). The majority of cases of PD appear to be sporadic, likely to be caused by a combination of genetic and environmental risk factors, the most evident being increasing age
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
