Autonomic dysreflexia and plasticity in mouse sympathetic preganglionic neurons after spinal cord injury Público

Abstract

Autonomic dysreflexia (AD), a neurological condition associated with spinal cord injury (SCI),
is associated with a loss of descending monoaminergic modulation on sympathetic output of the
autonomic nervous system. Plasticity of the central nervous system and specifically the spinal
cord is known to occur after injury, yet the anatomy of the mouse spinal cord post-SCI is
relatively unexplored. Using a mouse model of AD, distribution of serotonergic 5HT2A
receptors and dopaminergic D2 and D3 receptors were explored in control cords and following
chronic injury at high thoracic levels T1 or T2. Immunochemistry showed labeling of processes
adjacent to the intermediolateral nucleus (IML) for 5HT2A receptors and somatic/perisomatic
labeling of D2 and D3 receptors in the IML in control tissue. Post-SCI, all receptors showed
decreased expression close to the injury site (thoracic levels T2-T7) and dopaminergic receptors
D2 and D3 continued to show little to no expression further from the injury site (thoracic level
T9-T12). Serotonergic receptor 5HT2A showed increased expression in spinalized tissue in a
rostrocaudual gradient moving away from the injury site, with greatest expression in lowest
thoracic levels. Spinal cord plasticity was further demonstrated in the dorsal horn on injured
spinal cords with calcitonin gene-related peptide and Substance P staining, both heavily
implicated in pain perception. Presynaptic (D2, D3) and postsynaptic (5HT2A) modulation of
autonomic output could mediate AD symptoms, possibly with the use of a 5HT2A agonist for
treating effects due to colon distention and baclofen for spinal spasticity.

Table of Contents

Contents INTRODUCTION................................................................................................................................................1 Autonomic Dysreflexia .......................................................................................................................................1 Sympathetic preganglionic neurons .....................................................................................................................2 Monoamines.....................................................................................................................................................4 Immunochemical Approach .................................................................................................................................7 METHODOLOGY.................................................................................................................................................8 Surgical Transections .........................................................................................................................................8 Immunochemistry.............................................................................................................................................10 Microscopy and Analysis ....................................................................................................................................12 RESULTS.........................................................................................................................................................13 1. Dopamine receptors label both SPNs and MNs. ..................................................................................................13 2. Serotonergic 5HT2A receptors label processes adjacent to IML. ...........................................................................15

3. Effects of spinal cord transection on Dopamine D2 and D3 receptor expression. .....................................................16

DISCUSSION....................................................................................................................................................21 Acknowledgements...........................................................................................................................................23 References.......................................................................................................................................................24 Figures Figure 1: Autonomic Dysreflexia......................................................................................................................... 1 Figure 2: HBP/GFP labeling................................................................................................................................ 3 Figure 3: Autonomic Nervous System.................................................................................................................. 4 Figure 4: Descending Monoaminergic Pathways.................................................................................................... 5

Figure 5: Allen Database In Situ Hybridization...................................................................................................... 7

Figure 6: Surgical Transections........................................................................................................................... 9 Figure 7: Fluorogold/GFP Labeling...................................................................................................................... 11 Figure 8: Dopamine receptor labeling ................................................................................................................ 13

Figure 9: Serotonergic labeling; in vicinity of SPNs, with direct synapses via processes in IML.................................... 16

Figure 10: Dopaminergic labeling post-SCI; Expression lost throughout cord............................................................ 18

Figure 11: Serotonergic labeling post-SCI; Rostrocaudal gradient extends from injury site......................................... 20

Tables Table 1: D2 Receptor Fluorescence ......................................................................................................................17 Table 2: D3 Receptor Fluorescence ......................................................................................................................17 Table 3: 5HT2A Receptor Fluorescence .................................................................................................................21

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Palabra Clave	5ht2a receptor d3 receptor sympathetic preganglionic neurons d2 receptor mouse autonomic dysreflexia spinal cord injury
Committee Chair / Thesis Advisor	Hochman, Shawn, Emory University
Committee Members	Eisen, Arri, Emory University Starnes, Amanda, Emory University

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