Abstract Details

Title Developmental changes of the axon initial segment in animal model of Duchenne Muscular Dystrophy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 11-008

Objective Axon initial segment regulates anatomical polarity of the neuron (compartmentalization of axonal and somato-dendritic domains), subcellular polarity (compartmentalization of organelles in axons versus soma), and functional polarity (information flow and action potential initiation at the AIS). We investigated developmental changes in the axon initial segment (AIS) in mdx mouse model of Duchenne Muscular Dystrophy as the first step to understand the molecular underpinnings of neuronal circuit abnormalities in DMD.

Background

Neurons are highly polarized with multiple dendrites and a single axon. The scaffolding protein ankyrin G—restricted to the AIS in neurons—is the master regulator and organizer of the AIS, both in vitro and in vivo. Therefore, the AIS dictates the intrinsic excitability of a neuron and can be considered as one of the “molecular” determinant of cognition. The role of the AIS in DMD is unknown and forms the basis of this study.

Design/Methods We investigated developmental changes of the AIS at 1 month and 6 months in mdx52 mice and age- and sex-matched C57BL/6 controls (n=4 in each group) using immunohistochemistry and Western Blot. We also performed proximal ligation assay to study the location of sodium channels at the AIS. Behavioral paradigms, such as Open Field test and Y-Maze test, were used to assess memory- and anxiety were also performed.

Results Compared to controls, the length and diameter of the AIS is longer and thicker in mdx52 mice at 1-month of age, and at 6-months of age. While the AIS in controls normalizes at 6months, the AIS is persistently longer in mdx52 mice. Anxiety-like behavior was observed in mdx52 mice.

Conclusions The developmental abnormalities of the AIS in DMD suggests that neuronal circuit development and maintenance are affected. Strategies to mitigate AIS morphology could be used to target cognitive deficits in DMD

Authors/Disclosures
Samantha L. Shallop (VCU) PRESENTER	Mrs. Shallop has nothing to disclose.
	No disclosure on file
Mathula Thangarajh, MD, PhD, FAAN	Dr. Thangarajh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Thangarajh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for NS Pharma.

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