Forebrain Noradrenergic Alterations and Anxiety After Myocardial Infarction

227 Pages·2016·10.58 MB·English

LLooyyoollaa UUnniivveerrssiittyy CChhiiccaaggoo
LLooyyoollaa eeCCoommmmoonnss
Dissertations Theses and Dissertations
2012
FFoorreebbrraaiinn NNoorraaddrreenneerrggiicc AAlltteerraattiioonnss aanndd AAnnxxiieettyy AAfftteerr MMyyooccaarrddiiaall
IInnffaarrccttiioonn
Jaimee Glasgow
Loyola University Chicago
Follow this and additional works at: https://ecommons.luc.edu/luc_diss
Part of the Neurosciences Commons
RReeccoommmmeennddeedd CCiittaattiioonn
Glasgow, Jaimee, "Forebrain Noradrenergic Alterations and Anxiety After Myocardial Infarction" (2012).
Dissertations. 417.
https://ecommons.luc.edu/luc_diss/417
This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons.
It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more
information, please contact [email protected].
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright © 2012 Jaimee Glasgow
LOYOLA UNIVERSITY CHICAGO

FOREBRAIN NORADRENERGIC ALTERATIONS AND ANXIETY

AFTER MYOCARDIAL INFARCTION

A DISSERTATION SUBMITTED TO
THE FACULTY OF THE GRADUATE SCHOOL
IN CANDIDACY FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

PROGRAM IN CELL BIOLOGY, NEUROBIOLOGY, AND ANATOMY

BY
JAIMEE ELIZABETH GLASGOW

CHICAGO, ILLINOIS
AUGUST 2012
ACKNOWLEDGEMENTS
First and foremost, I would like to thank my advisor, Karie Scrogin, for her
boundless knowledge and patience. Throughout my training, she has
encouraged and challenged me to grow as a scientist, and in all areas of my life.
I would also like to thank the other members of my dissertation committee, Dr. EJ
Neafsey, Dr. Kuei Tseng, Dr. George Battaglia, Dr. Wendy Kartje, and Dr.
Thackery Gray, for their time and thoughtful input throughout my studies.
Finally, I would like to thank my friends and family for their contribution to this
research through their unconditional love and support. I would especially like to
thank my mother, Peggy Glasgow, for her unwavering encouragement until
her final days.
i
TABLE OF CONTENTS
ACKNOWLEDGEMENTS ...................................................................................... i

LIST OF TABLES ................................................................................................. iv

LIST OF FIGURES ............................................................................................... v

LIST OF ABBREVIATIONS ................................................................................. vii

CHAPTER 1: INTRODUCTION ............................................................................ 1

CHAPTER 2: REVIEW OF RELATED LITERATURE ......................................... 10
Anxiety and Depression after MI and in Heart Failure ................................... 10
Assessments of Depression and Anxiety ...................................................... 12
Neural Control of the Normal and Failing Heart ............................................ 17
Normal Cardiac Function ......................................................................... 17
Autonomic Nervous System: Overview .................................................... 19
Myocardial Infarction and Heart Failure ................................................... 22
Autonomic Nervous System in MI and Heart Failure ............................... 23
The Endocrine System in MI and Heart Failure ....................................... 24
Arrhythmia Generation After MI ..................................................................... 26
Emotional Stressors, Sympathetic Activation, and Arrhythmia ...................... 27
Cortical and Subcortical Control of Heart Rhythms ....................................... 29
Central Nervous System Pathways Mediating Stress Responses ................ 30
Amygdala ................................................................................................. 30
Central Nucleus ....................................................................................... 31
Intercalated Cell Masses .......................................................................... 32
Intra-Amygdala Circuitry in Conditioned Fear .......................................... 33
Prefrontal Cortex: Anatomy and Regulation of Stress Responses ................ 34
Medial Prefrontal Cortex: Anatomy and Role in Stress Responses ......... 34
Insular Cortex .......................................................................................... 38
Orbitofrontal Cortex ................................................................................. 39
Prefrontal Cortex-Amygdala Interactions....................................................... 40
Central Noradrenergic Regulation of Stress Responses and Circulation ...... 41
Locus Coeruleus ...................................................................................... 41
Central Noradrenergic Control of Circulation................................................. 43
Noradrenergic Modulation of Stress Responses ........................................... 45

ii
CHAPTER 3: NEOPHOBIA, ARRHYTHMIA, AND ALTERED FOREBRAIN
METABOLIC ACTIVITY AFTER MYOCARDIAL INFARCTION .................... 49
Abstract: ........................................................................................................ 49
Introduction: .................................................................................................. 50
Materials and Methods: ................................................................................. 54
Results: ......................................................................................................... 65
Discussion ..................................................................................................... 88

CHAPTER 4: ALTERATIONS IN BETA-ADRENERGIC RECEPTORS AFTER
MYOCARDIAL INFARCTION...................................................................... 100
Abstract: ...................................................................................................... 100
Introduction: ................................................................................................ 101
Materials and Methods: ............................................................................... 105
Discussion ................................................................................................... 127

CHAPTER 5: ALTERATIONS IN EXPRESSION AND EXTINCTION OF
CONDITIONED FEAR AFTER MYOCARDIAL INFARCTION .................... 134
Abstract ....................................................................................................... 134
Introduction ................................................................................................. 135
Materials and Methods ................................................................................ 139
Results ........................................................................................................ 148
Discussion ................................................................................................... 172

GENERAL DISCUSSION ................................................................................. 181

REFERENCE LIST ........................................................................................... 190

VITA ................................................................................................................. 216
iii
LIST OF TABLES
Table 1. Cytochrome oxidase activity (NS). 87
Table 2. Specific 125ICYP binding in prefrontal cortical and amygdala regions. 125
Table 3. Isoproterenol inhibition of 125ICYP binding. 126
iv
LIST OF FIGURES
Figure 1. Coronary artery ligation surgery 69
Figure 2. Left ventricular function (Specific Aim 1) 70
Figure 3. Locus coeruleus stimulation parameters 72
Figure 4. Terminal measures of congestion and remodeling (Specific Aim 1) 73
Figure 5. Open field test for anxiety and neophobia 74
Figure 6. Blood pressure and heart rate responses to locus coeruleus
stimulation 75

Figure 7. Representative arrhythmia waveforms 77
Figure 8. ECG and arterial pressure during locus coeruleus stimulation 78
Figure 9. Sequential ECG waveforms 79
Figure 10. Quantification of locus coeruleus stimulation-associated arrhythmias 80
Figure 11. Incubation curve for cytochrome oxidase histochemistry 81
Figure 12. Representative sections showing cytochrome oxidase staining 82
Figure 13. Cytochrome oxidase activity 84
Figure 14. Cytochrome oxidase activity: ipsi- vs. contralateral infralimbic cortex 86
Figure 15. Schematics of incubations to determine specific binding 116
Figure 16. Schematics of 125ICYP solutions to determine agonist inhibition of
β AR binding 118
1

Figure 17. Left ventricular function (Specific Aim 2) 120
Figure 18. Terminal measures of congestion and remodeling (Specific Aim 2) 121
v
Figure 19. Typical 125ICYP autoradiograms used to determine βAR binding in the
prefrontal cortex 122

Figure 20. Standard curves relating specific activity and optical density 123
Figure 21. Typical 125ICYP autoradiograms used to determine βAR binding in the
amygdala 124

Figure 22. Left ventricular function (Specific Aim 3) 153
Figure 23. Terminal measures of congestion and remodeling (Specific Aim 3) 155
Figure 24. Freezing responses during fear conditioning 156
Figure 25. Freezing responses during fear extinction 158
Figure 26. Blood pressure responses during extinction 161
Figure 27. Change in blood pressure during extinction 162
Figure 28. Heart rate responses during extinction 163
Figure 29. Change in heart rate during extinction 164
Figure 30. Freezing responses during extinction recall 165
Figure 31. Blood pressure responses during extinction recall 167
Figure 32. Change in blood pressure in extinction recall 168
Figure 33. Heart rate responses during extinction recall 169
Figure 34. Change in heart rate during extinction recall 170
Figure 35. Defecation response during extinction and extinction recall 171
Figure 36. Conclusions and model 188
vi
LIST OF ABBREVIATIONS

α AR Alpha2-adrenergic receptor
2
AP Arterial pressure
AV Atrioventricular
ACE Angiotensin-converting enzyme
ACTH Adrenocorticotropic hormone
AVP Arginine vasopressin
βAR Beta-adrenergic receptor
β AR Beta1-adrenergic receptor
1
β AR Beta2-adrenergic receptor
2
BLAc Basolateral complex of the amygdala
BLA Basolateral nucleus of the amygdala
cAMP Cyclic adenosine monophosphate
CAL Coronary artery ligation
CeA Central nucleus of the amgydala
CeL Central amygdala: lateral division
CeM Central amygdala: medial division
Cg Anterior cingulate cortex
CN Central nervous system
CO Cytochrome oxidase
vii
CS Conditioned stimulus
DPM Decays per minute
ECG Electrocardiogram
EPM Elevated plus maze
FO Fractional occupancy
FS Fractional shortening
Gαi G inhibitory protein
Gαs G stimulatory protein
GABA Gamma-aminobutyric acid
GPCR G protein-coupled receptor
HPA Hypothalamic-pituitary-adrenal
HPLC High-performance liquid chromatography
HR Heart rate
ICM Intercalated cell masses
125ICYP 125-Iodocyanopindolol
IL Infralimbic cortex
Ins Insular cortex
LVDD Left ventricular diastolic diameter
M Motor cortex
MAP Mean arterial pressure
OF Orbitofrontal cortex
PKA Protein kinase A
viii