Microglial morphology: what we can learn about neuroinflammation and Huntington’s Disease Marley Realing.

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Microglial morphology: what we can learn about neuroinflammation and Huntington’s Disease Marley Realing

Microglia: Cause or Response to Neuroinflammation? Microglial are resident brain immune cells Activation state can be studied using morphology They both induce and react to neruroinflammation It has been shown there is a significant amount of microglia activation in HD and other neurodegenerative disease The role of microglial activation in neurodegeneration is unclear In health In disease

IBA-1 labels Brain Microglial A-B: anti-IBA1 antibody (Wako Chemical) 1:500 anti-IBA1 No primary control C-D: anti-IBA1 antibody (Santa Cruz) C) 1:500 anti-IBA1 D) anti-IBA1 + blocking peptide Optimization of staining Wako out perfromed Santa cruz

Four Microglia Morphologies were Identified Ramified: small cell body, ramified processes Primed: larger, more irregularly shaped cell body Reactive: large cell body and retracted processes Ameboid: enlarged cell body and few, if any processes Varied morphologies based on activation state Scale bars = 20 mm

Wild Type infected with Toxoplasma gondii Huntington’s Disease and T. gondii Change Microglial Morphology in the Cortex Wild Type infected with Toxoplasma gondii Wild-type Huntington’s disease C Different genotypes/ situations looking at difference in microglia morphologies A- surveilling/ramififed with long processes B- aeboid with retracted processes- reactive to environmental change( aka huntington’s disease) c) A positive control WT brain infected with T. gondii- Highly reactive, with a lot of activation (large dark cell bodies, with a few processes) Scale bars = 20 mm

Conclusions and Future Directions Microglia morphology differed in mice with HD compared to control wild-type mice Wild-type mice with Toxoplasma gondii infection due increases in number, staining intensity, and morphological changes Future plans: Studying microglial morphology after HD-potentiating iron treatment Quantitatively differentiate morphology using Neuroleucida software Staining was optimized 1:250 and 1;500 concentrations Wako more specific than Santa Cruz Parasite infection showed heavily increased number of microglia and alteration in morphology Now that we have a staining procedure optimized

Acknowledgements Thank you to: Wyoming INBRE fellowship for the Spring and Summer of 2017 Advisor: Dr. Jonathan Fox and David Donley Lab Members: Sonal Agrawal, Julia Fox, Ashton Abarr, Gabrielle