The effect of treadmill training on synaptic stripping from axotomized motoneurons in mice Open Access

Abstract

Abstract
The effect of treadmill training on synaptic stripping from axotomized motoneurons in
mice
By Joseph R. Krakowiak, Jr.
Functional recovery following peripheral nerve injury is poor despite the fact that
axons in peripheral nerves can regenerate robustly. A potential cause for poor functional
recovery that is not widely appreciated is 'synaptic stripping': the elimination of synaptic
inputs from the soma and proximal dendrites of motoneurons in the spinal cord following
peripheral nerve injury. The molecular mechanism and signaling pathways of synaptic
stripping are currently unknown. However, recent work has provided a case for the
dependence on neurotrophins, especially brain derived neurotrophic factor (BDNF).
Modest treadmill training has been shown to stimulate neuronal production of BDNF and
NT-4/5. In this thesis, I used modest treadmill training in mice to increase BDNF in
motoneurons in an attempt to prevent or counter synaptic stripping following a peripheral
nerve injury. I found that with treadmill training after a peripheral nerve injury, nearly no
synaptic stripping effect was observed compared to untrained mice. I repeated the
treadmill training experiments with complete BDNF knockout mice and neuron-specific
BDNF knockouts. In complete BDNF knockout mice, treadmill training produced a much
smaller effect, and in neuron-specific BDNF knockout mice, treadmill training produced
no effect. In fact, the opposite effect was observed resulting in more synaptic stripping
after training compared to untrained mice. This thesis provides support for the hypothesis
that BDNF plays an integral role in the synaptic reformation caused by treadmill training.

Table of Contents

TABLE OF CONTENTS


Background ............................................................................................................1

Methods..................................................................................................................5
Animals and Surgical Methods ......................................................................................5
Tamoxifen Treatment..................................................................................................7
Treadmill Training Procedures ......................................................................................7
Immunohistochemical Analysis .....................................................................................8
Imaging Analysis .......................................................................................................8
Statistical Analysis ....................................................................................................9

Results ..................................................................................................................10
Synaptic stripping following sciatic nerve transection in the mouse ....................................10
Treadmill training prevents synaptic stripping .................................................................11
An astrocyte reaction is absent after treadmill training ....................................................11
Lack of BDNF prevents treadmill training effect ..............................................................12
Lack of neuronal BDNF prevents treadmill training effect ..................................................13
Treadmill training effect is dependent upon BDNF ...........................................................13

Discussion .............................................................................................................14

Future Directions ...................................................................................................17

References ............................................................................................................18

Figures and Legends ...............................................................................................22
Figure 1 ..................................................................................................................22
Figure 2 ..................................................................................................................23
Figure 3 ..................................................................................................................24
Figure 4 ..................................................................................................................25
Figure 5 ..................................................................................................................26
Figure 6 ..................................................................................................................27
Figure 7 ..................................................................................................................28
Figure 8 ..................................................................................................................29
Figure 9 ..................................................................................................................30
Figure 10 ................................................................................................................31
Figure 11 ................................................................................................................32
Figure 12 ................................................................................................................33

About this Honors Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Rehabilitation and Therapy Biology, Cell
Keyword	treadmill nerve synaptic stripping training exercise BDNF mice
Committee Chair / Thesis Advisor	English, Arthur W, Emory University
Committee Members	Liu, Robert C, Emory University Crutcher, Michael D, Emory University

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