Parkinson’s Disease-related LRRK2 Regulates the Compartmentation of Murine StriatumCharlesice Hawkins, Michael Segev, Wang Zheng, Chengsong Xie, Jinhui Ding, and Huaibin Caicchawkin@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 striatumBottom Row: 3D reconstructions of striosome compartment. Quantification shown in the figures to the right.

+/+ -/- R1441C/R1441C

+/+ -/- R1441C/R1441C

Parkinson’s Disease (PD)