hawkins ugsp nih 20150730 poster final
TRANSCRIPT
Parkinson’s Disease-related LRRK2 Regulates the Compartmentation of Murine StriatumCharlesice Hawkins, Michael Segev, Wang Zheng, Chengsong Xie, Jinhui Ding, and Huaibin [email protected]
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)