Effects of adolescent alcohol binge drinking on prefrontal myelin

166 Pages·2017·8.84 MB·English

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Doctoral Dissertations Dissertations and Theses
November 2016
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Wanette M. Vargas-Rodriguez
University of Massachusetts Amherst
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Vargas-Rodriguez, Wanette M., "Effects of adolescent alcohol binge drinking on prefrontal myelin" (2016).
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EFFECTS OF ADOLESCENT ALCOHOL BINGE DRINKING ON
PREFRONTAL MYELIN

A Dissertation Presented

by

WANETTE M. VARGAS RODRIGUEZ

Submitted to the Graduate School of the
University of Massachusetts Amherst in partial fulfillment
of the requirements for the degree of

DOCTOR OF PHILOSOPHY

September 2016

Neuroscience and Behavior Graduate Program
© Copyright by Wanette M. Vargas Rodriguez 2016

All Rights Reserved
EFECTS OF ADOLESCENT ALCOHOL BINGE DRINKING ON PREFRONTAL
MYELIN

A Dissertation Presented

by

WANETTE M. VARGAS RODRIGUEZ

Approved as to style and content by:

__________________________________________
Heather N. Richardson, Chair

__________________________________________
Elizabeth A. Connor, Member

__________________________________________
David Moorman, Member

_________________________________________
R. Thomas Zoeller, Member

_________________________________________
Rebecca Spencer, Graduate Program Director
Neuroscience and Behavior Program

_________________________________________
Elizabeth R. Dumont, Director
Interdisciplinary Graduate Programs, CNS
DEDICATION

To:
my amazing and loving husband, Michael Hany Riad;
my wonderful super-woman mother Wanda Ivette Rodríguez;
my awesome father Elmo Vargas;
my dear granny Zoraida Bermúdez.

Thank you all for your continuous and unconditional love and support.

I love you all very much.
ACKNOWLEDGMENTS
I would like to thank my wonderful advisor, Dr. Heather N. Richardson for giving
me the opportunity to work with her and for all her guidance and support. Heather has
been more than an advisor; she has been my mentor throughout this time, teaching me
valuable lessons not only about science and career, but also about life. Thank you to my
amazing committee, Dr. Elizabeth A. Connor, Dr. David Moorman, and Dr. R. Thomas
Zoeller, for their insightful feedback, support, scientific guidance, and encouragement.
I am grateful of Lynn Bengston for her help with experiments, training, and
written feedback. I thank current and past lab members: Kristie Fierro, Chrisanthi
Karanikas, Dr. Yi-Ling Lu, Dr. Jesse McClure, and Andrea Silva-Gotay for their
feedback, help, and support. They are lab mates and friends. I am also very thankful for
all the undergraduate students that worked with me, especially, Sean McDougall, Aditi
Dave, Divya Harpalani, Ryan Tressel, Callie Dacyczyn, Azinne Zarrabi, Kyle O’Donnell,
and Frank Jackson.
I would like to extend my appreciation to Dr. Brian Whitcomb for his support and
expert advice on statistical tests, Dr. Jerrold Meyer for his expert guidance on the
oxidative stress experiments, Dr. Geng-Lin Li for collaborating with our lab for the
electrophysiology experiments, Dr. Samuel Hazen for his assistance with the RT-qPCR
experiments, Dr. Peter Chien and lab for lending us their spectrophotometer, Dr. Nicholas
Gilpin and Dr. Maury Cole for their help with some experiments, and to Dr. Luke
Remage-Healey for critical reading of our manuscript.
I would also like to thank animal care personnel, especially Ed Golembeski for all
their help with the animals. Thank you also to the Neuroscience and Behavior program,
v
its director Dr. Rebecca Spencer, GOC chair Dr. Gerald Downes, and managers (Maggie
DeGregorio, Vickie Rupp, Susan Capistran, Linda Witt), and NSB friends for being such
a supportive group. A special thanks to NEAGEP (Dr. Sandy Petersen, Dr. Vanessa Hill,
Dr. Heyda Martinez, and Dr. Marlina Duncan) for the NEAGEP fellowship and for
providing a community of support and encouragement. This research was partially
supported by a Dissertation Research Grant from the University of Massachusetts
Amherst to WMV.
Lastly, I want to thank God for blessing me always, and my parents, Elmo and
Wanda, my husband Michael, and my family and friends for their unconditional love and
support. My mother is my motivation and role model. Michael shares with me a love for
neuroscience and has been so kind, loving, and patient. I truly admire him. Thank you all
for believing in me.
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ABSTRACT
EFFECTS OF ADOLESCENT ALCOHOL BINGE DRINKING ON
PREFRONTAL MYELIN

SEPTEMBER 2016

WANETTE M. VARGAS RODRIGUEZ, B.A., UNIVERSITY OF PUERTO RICO
MAYAGUEZ

Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST

Directed by: Professor Heather N. Richardson

Alcohol binge drinking is highly prevalent in teenagers and is associated with various
harmful health effects and social problems. During adolescence, brain regions such as the
prefrontal cortex (PFC) are still undergoing active development, characterized by
increases in white matter volume. While the morphological details and the cellular and
molecular sequences governing adolescent white matter development are not fully
known, it is known that this development process is sensitive and can be disrupted.
Although consumption of alcohol in a binge drinking pattern has been linked to lower
white matter integrity in humans, it is important to determine if alcohol is causing this
change or if predisposing factors can influence drinking. A rodent model of voluntary
binge drinking was used to elicit high alcohol intake during a short developmental
window in adolescence. Myelin was then assessed using several histochemical measures.
Results showed that adolescent development is marked by an increase in myelinated
fibers in the PFC that accompanied an increase in conduction velocity, and alcohol
reduces prefrontal white matter and myelinated fiber density. In addition, heavy drinking
was associated with long-term cognitive deficits. I also investigated sex differences in the
effects of adolescent alcohol consumption on PFC myelination, showing that males
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appear to be more vulnerable than females. The findings altogether increase our
understanding of the developmental process of prefrontal myelination in adolescence and
the maladaptive effects alcohol can have on this critical process.
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TABLE OF CONTENTS
Page

ACKNOWLEDGMENTS .................................................................................................. v
ABSTRACT ...................................................................................................................... vii
LIST OF TABLES ............................................................................................................ xii
LIST OF FIGURES ......................................................................................................... xiii
CHAPTER
1. GENERAL INTRODUCTION AND BACKGROUND ................................................ 1
1.1 Alcohol, adolescent consumption pattern, and consequences .......................... 1
1.2 White matter and myelination ........................................................................... 4
1.3 Prefrontal cortex ................................................................................................ 9
1.4 Effects of adolescent alcohol consumption on the prefrontal cortex .............. 14
1.5 Effects of adolescent alcohol consumption on frontal white matter ............... 15
1.6 Objectives ....................................................................................................... 17
1.7 References ....................................................................................................... 18
2. MYELINATION OF PREFRONTAL AXONS IS ACCOMPANIED BY
INCREASED SPEED AND INTEGRITY OF CORTICAL
NEUROTRANSMISSION IN RATS ............................................................................... 31
2.1 Abstract ........................................................................................................... 31
2.2 Introduction ..................................................................................................... 32
2.3 Materials and Methods .................................................................................... 36
2.4 Results ............................................................................................................. 41
2.5 Discussion ....................................................................................................... 44
2.6 Figures and Tables .......................................................................................... 52
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