1. Parkinson’s Disease-related LRRK2 Regulates the
Compartmentation of Murine Striatum
Charlesice Hawkins, Michael Segev, Wang Zheng, Chengsong Xie, Jinhui Ding, and Huaibin Cai
cchawkin@gmail.com
Introduction Results
Methods
LRRK2 Functions3
• Vesicle Endocytosis
• Protein Synthesis
• Cytoskeletal Growth
• Synaptogenesis
• Lysosome & Autophagy
• Golgi Sorting
R1441C
Substantia Nigra-pc (SNpc)
Dopaminergic neurons are
lost in PD
SNpc
Matrix
Striatum
We hypothesize that striosome structures
will change in LRRK2 mouse models
Mice
+/+ -/-
R1441C/
R1441C
Nr4a1-eGFP striosomal
marker
Discussion
The Laboratory of Neurogenetics, Wang Zheng, PhD, Michael Segev,
Lisa Chang, Jenny Wang, Hannah Wang, Xi Chen, PhD, Carmelo Sgobio,
PhD, Lixin Sun, PhD, Junbing Wu, PhD, Jia Yu, MDPhD OITE, Rayna
Truelove, PhD, Darryl Murray, PhD, Erika Barr, PhD, Sharon Milgram, PhD
1. Fujiyama F, Takahashi S, Karube F. Morphological elucidation of basal ganglia circuits contributing reward prediction. Frontiers in
neuroscience. 2015;9.
2. Mandemakers W, Snellinx A, O'Neill MJ, De Strooper B. LRRK2 expression is enriched in the striosomal compartment of mouse
striatum. Neurobiol Dis. 2012;48(3):582-593.
3. Martin I, Kim JW, Dawson VL, Dawson TM. LRRK2 pathobiology in Parkinson's disease. J Neurochem. 2014;131(5):554-565.
4. http://ghr.nlm.nih.gov/gene/LRRK2
N=2
• We speculate that the striosome compartment is structurally
reorganizing
• The highly irregular 3D nature of striosome compartments pose a
significant challenge in characterizing them
• Future studies will include a larger sample size and the most
common familial PD mutation G2019S
• Improve image analysis
References & Acknowledgments
Substantia Nigra
Start End
1. Photoshop
- Extract Striatum
- Consistency Improvement
2. Voloom
- Alignment
3. Imaris
- 3D Reconstruction
- Quantification
LRRK2 Mutations
LRRK2 is more
enriched in striatal
striosome
compartments2
LRRK2 missense
mutations causes
familial Parkinson’s
disease3,4
Striosome
1
Significant differences in the volume
distribution of striosomes were not
observed
The volume ratio of striosome
compartments seems enlarged in KO
mice, but not statistically significant.
Top Row: Example 2D sections. Green arrows show the region that we suspect is changing in
the -/- and R1441C/R144C striatum
Bottom Row: 3D reconstructions of striosome compartment. Quantification shown in the
figures to the right.
+/+ -/- R1441C/R1441C
+/+ -/- R1441C/R1441C
Parkinson’s Disease (PD)