Resume

• 2007

  Ruth L Kirschstein Predoctoral Fellow (F31)

  investigated the contributions of environmental and genetic disruption of circadian rhythms to alcohol-seeking behavior

  National Institute on Alcoholism and Alcohol Abuse

  NIH Loan Repayment Program

  investigates the contributions of genetic and gonadal sex to sleep homeostasis

  National Institute of Minority and Health Disparities

  Doctor of Philosophy (PhD)

  Biological Sciences

  Physiology

  Sleep Research Society Trainee Member-At-Large \nSLEEP 2009 and 2010 Trainee Day Planning Committee\nNational Sleep Foundation Educational Advocate\nBiology Graduate Student Council

  Past President and Vice President

  Kent State University

  B.s.

  Division I Track and Field: 4 year varsity letterman\nStudent Athlete Advisory Board: Publicity Chair

  Psychology

  Division I Track and Field

  Feminist Majority Leadership Alliance

  Student Athlete Advisory Board

• 1.0

  \nAlcohol dependence is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting

  suggesting a mode for the disruptive effect of alcohol dependence on the circadian timing system. We extend previous work in C57BL/6J mice to: (i) characterize the suprachiasmatic nucleus (SCN) pharmacokinetics of acute systemic ethanol administration

  (ii) explore the effects of acute ethanol on photic and nonphotic phase-resetting

  and (iii) determine if the SCN is a direct target for photic effects.\nFirst

  microdialysis was used to characterize the pharmacokinetics of acute intraperitoneal (i.p.) injections of 3 doses of ethanol (0.5

  and 2.0 g/kg) in the mouse SCN circadian clock. Second

  the effects of acute i.p. ethanol administration on photic phase delays and serotonergic ([+]8-OH-DPAT-induced) phase advances of the circadian activity rhythm were assessed. Third

  the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized.\nPeak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20 to 40 minutes postinjection with half-lives for clearance ranging from 0.6 to 1.8 hours. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase delays.\nCONCLUSIONS:\nThese results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and nonphotic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral

  physiological

  and endocrine rhythms associated with alcoholism.

  Acute ethanol disrupts photic and serotonergic circadian clock phase-resetting in the mouse

  The PER2 clock gene modulates ethanol consumption

  such that mutant mice not expressing functional mPer2 have altered circadian behavior that promotes higher ethanol intake and preference. Experiments were undertaken to characterize circadian-related behavioral effects of mPer2 deletion on ethanol intake and to explore how acamprosate (used to reduce alcohol dependence) alters diurnal patterns of ethanol intake. Male mPer2 mutant and WT (wild-type) mice were entrained to a 12:12 h light-dark (12L:12D) photocycle

  and their locomotor and drinking activities were recorded. Circadian locomotor measurements confirmed that mPer2 mutants had an advanced onset of nocturnal activity of about 2 h relative to WTs

  and an increased duration of nocturnal activity (p < .01). Also

  mPer2 mutants preferred and consumed more ethanol and had more daily ethanol drinking episodes vs. WTs. Measurements of systemic ethanol using subcutaneous microdialysis confirmed the advanced rise in ethanol intake in the mPer2 mutants

  with 24-h averages being ∼60 vs. ∼25 mM for WTs (p < .01). A 6-day regimen of single intraperitoneal (i.p.) acamprosate injections (300 mg/kg) at zeitgeber time (ZT) 10 did not alter the earlier onset of nocturnal ethanol drinking in the mPer2 mutants

  but reduced the overall amplitude of drinking and preference (both p < .01). Acamprosate also reduced these parameters in WTs. These results suggest that elevated ethanol intake in mPer2 mutants may be a partial consequence of an earlier nighttime activity onset and increase in nocturnal drinking activity. The suppressive action of acamprosate on ethanol intake is not due to an altered diurnal pattern of drinking

  but rather a decrease in the number of daily drinking bouts and amount of drinking per bout.

  Circadian and acamprosate modulation of elevated ethanol drinking in mPer2 clock gene mutant mice

  Acamprosate suppresses alcohol intake and craving in recovering alcoholics; however

  the central sites of its action are unclear. To approach this question

  brain regions responsive to acamprosate were mapped using acamprosate microimplants targeted to brain reward and circadian areas implicated in alcohol dependence. mPer2 mutant mice with nonfunctional mPer2

  a circadian clock gene that gates endogenous timekeeping

  were included

  owing to their high levels of ethanol intake and preference. Male wild-type (WT) and mPer2 mutant mice received free-choice (15%) ethanol/water for 3 wk. The ethanol was withdrawn for 3 wk and then reintroduced to facilitate relapse. Four days before ethanol reintroduction

  mice received bilateral blank or acamprosate-containing microimplants releasing ∼50 ng/day into reward [ventral tegmental (VTA)

  peduculopontine tegmentum (PPT)

  and nucleus accumbens (NA)] and circadian [intergeniculate leaflet (IGL) and suprachiasmatic nucleus (SCN)] areas. The hippocampus was also targeted. Circadian locomotor activity was measured throughout. Ethanol intake and preference were greater in mPer2 mutants than in wild-type (WT) mice (27 g·kg(-1)·day(-1) vs. 13 g·kg(-1)·day(-1) and 70% vs. 50%

  respectively; both

  P < 0.05). In WTs

  acamprosate in all areas

  except hippocampus

  suppressed ethanol intake and preference (by 40-60%) during ethanol reintroduction. In mPer2 mutants

  acamprosate in the VTA

  PPT

  and SCN suppressed ethanol intake and preference by 20-30%. These data are evidence that acamprosate's suppression of ethanol intake and preference are manifest through actions within major reward and circadian sites.

  Acamprosate-responsive brain sites for suppression of ethanol intake and preference

  The mPer2 clock gene modulates cocaine actions in the mouse circadian system

  Adam Stowie

  Cocaine is a potent disruptor of photic and non-photic pathways for circadian entrainment of the master circadian clock of the suprachiasmatic nucleus (SCN). These actions of cocaine likely involve its modulation of molecular (clock gene) components for SCN clock timekeeping. At present

  however

  the physiological basis of such an interaction is unclear. To address this question

  we compared photic and non-photic phase-resetting responses between wild-type (WT) and Per2 mutant mice expressing nonfunctional PER2 protein to systemic and intra-SCN cocaine administrations. In the systemic trials

  cocaine was administered i.p. (20 mg/kg) either at midday or prior to a light pulse in the early night to assess its non-photic and photic behavioral phase-resetting actions

  respectively. In the intra-SCN trial

  cocaine was administered by reverse microdialysis at midday to determine if the SCN is a direct target for its non-photic phase-resetting action. Non-photic phase-advancing responses to i.p. cocaine at midday were significantly (∼3.5-fold) greater in Per2 mutants than WTs. However

  the phase-advancing action of intra-SCN cocaine perfusion at midday did not differ between genotypes. In the light pulse trial

  Per2 mutants exhibited larger photic phase-delays than did WTs

  and the attenuating action of cocaine on this response was proportionately larger than in WTs. These data indicate that the Per2 clock gene is a potent modulator of cocaine's actions in the circadian system. With regard to non-photic phase-resetting

  the SCN is confirmed as a direct target of cocaine action; however

  Per2 modulation of this effect likely occurs outside of the SCN.

  The mPer2 clock gene modulates cocaine actions in the mouse circadian system

  Here

  EtOH drinking and preference were measured in groups of aged Syrian hamsters. Further

  because voluntary exercise (wheel-running) is a rewarding substitute for EtOH in young adult hamsters

  the potential for such reward substitution was also assessed.Aged (24 month-old) male hamsters were subjected to a three-stage regimen of free-choice EtOH (20% v/v) or water and unlocked or locked running wheels to investigate the modulatory effects of voluntary wheel running on EtOH intake and preference. Levels of fluid intake and activity were recorded daily across 60 days of experimentation.Prior to wheel running

  levels of EtOH intake were significantly less than levels of water intake

  resulting in a low preference for EtOH (30%). Hamsters with access to an unlocked running wheel had decreased EtOH intake and preference compared with hamsters with access to a locked running wheel. These group differences in EtOH intake and preference were sustained for up to 10 days after running wheels were re-locked.

  Impact of wheel running on chronic ethanol intake in aged Syrian hamsters

  I am a neurobiologist with expertise in sleep and circadian rhythms for the United States Army (active duty). I have worked with human and animal models of study. This work has examined sleep and activity regulatory mechanisms as well as adaptation and resiliency to environmental stressors such as exercise

  jet lag

  and sleep deprivation. I have undertaken several leadership and service positions for the federal government

  professional research societies

  and university departments. At present

  I sit on the Federal Fatigue Management Working Group and have contributed to Army Doctrine on Holistic Health and Fitness through the Office of the Surgeon General. I also serve on the NCAA task force for mental health

  having contributed to the first edition of the NCAA student-athlete mental health handbook to include recommendations for better sleep hygiene. I consult with US Olympic

  collegiate

  and professional sporting teams and major police and fire departments (e.g.

  NYPD

  Boston) in preparation for travel and to create sleep friendly environments. I have also served on the Board of Directors of the Sleep Research Society and presently chair a public advocacy committee for the Society for Research on Biological Rhythms. I have written op-ed and column pieces for Science and professional society bulletins. I have a popular science book entitled Meathead: Unraveling the Athletic Brain on bookshelves that bridges my athletic career with peer-reviewed research in neuroscience and exercise physiology.

  Allison

  Brager

  Morehouse College

  Kent State University

  Walter Reed Army Institute of Research

  Morehouse School of Medicine

  Cuyahoga Falls City Schools

  US Army Warrior Fitness Training Center

  Bradley Sleep and Chronobiology Laboratory

  Kent

  OH

  My dissertation and collaborative projects investigated the neurobiology of alcoholism through the exploration of alcohol's effects on circadian and reward systems

  molecular regulation of alcohol drinking rhythms

  and influences of the circadian system on the efficacy of an anti-relapse pharmaceutical. All of this work was completed in transgenic mice.

  Doctoral Student

  Kent State University

  Silver Spring

  Maryland

  Projects related to optimizing physical and mental performance in the nation's warriors.

  National Research Council Fellow

  Walter Reed Army Institute of Research

  Atlanta

  Georgia

  My research focuses on homeostatic and neuroenodcrine systems (sleep/circadian rhythms) at behavioral and physiological levels of study.

  Postdoctoral Fellow

  Morehouse School of Medicine

  Chief of Sleep Research Center

  Federal Fatigue Management Working Group

  Holistic Health Working Group with Office of the Surgeon General

  Level 1 Defense Acquisitions

  Walter Reed Army Institute of Research

  Cuyahoga Falls City Schools

  Cuyahoga Falls

  OH

  I was the pole vault

  long jump

  and high jump coach of both the boys' and girls' high school teams. Several of my athletes have qualified and have set records at district

  regional

  and state track and field tournaments and are on athletic scholarships at Division I universities.

  Assistant Track Coach

  I assisted graduate students and technicians with various human sleep and circadian studies

  including; \n1) assessing delayed sleep phases in adolescents \n2) characterizing alcohol's effects on sleepiness

  sleep architecture

  and circadian physiology in young adults \n3) participating in a clinical trial for a prospective sleeping aid in the elderly and\n4) collecting pilot data for a grant aimed to study the co-morbidity of sleep-disordered breathing and ADHD in children.

  Bradley Sleep and Chronobiology Laboratory

  US Army Warrior Fitness Training Center

  Fort Knox

  KY

  Special outreach mission of the Army recruiting command to support elite athletic endeavors of active duty soldiers and future research & development of human performance technology and training programs.

  Athlete and Director of Human Performance Operations and Outreach Education

  I coach the individual and decathlete pole vault. The team is seven times back-to-back conference champs and has had several athletes qualify for the NCAA tournament.

  Morehouse College

  Adjunct

  I co-teach the neural systems and behavior course offered to upperclassmen.

  Morehouse College

  Published Author

  Off-Colored Rainbows

  young adult fiction\n\nhttp://www.amazon.com/Off-Colored-Rainbows-Allison-Brager-ebook/dp/B00N1K6O56/ref=sr_1_1?s=books&ie=UTF8&qid=1411089671&sr=1-1&keywords=allison+brager

  Ruth L Kirschstein Postdoctoral Fellow (F32)

  investigates peripheral regulation of sleep homeostasis

  namely focused on skeletal muscle

  National Institute of Heart

  Lung

  and Blood

  Author of Meathead: Unraveling the Athletic Brain

  A popular science book debunking the myth of the \"dumb jock\". Available as ebook

  softcover

  and hardcover. \n\nhttp://www.amazon.com/Meathead-Unraveling-Athletic-Allison-Brager/dp/149086444X/ref=sr_1_1?ie=UTF8&qid=1426175702&sr=8-1&keywords=Meathead

• Public Speaking

  Program Evaluation

  PowerPoint

  Research

  Statistics

  Higher Education

  Immunohistochemistry

  Neuroscience

  Grant Writing

  SPSS

  Assay Development

  Fundraising

  Microsoft Office

  Teaching

  Physiology

  Sleep loss and the inflammatory response to chronic environmental circadian disruption in mice

  Alec Davidson

  Patrick Delisser

  Divya Natarajan

  Oscar Castanon-Cervantes

  J. Christopher Ehlen

  Here

  we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD)

  and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD

  in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week

  resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc)

  basal forebrain (BF)

  and medial preoptic area (MnPO). To assess the inflammatory response

  trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc

  BF

  and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD

  but not mice subjected to IW. Thus

  the net sleep loss that occurs under ECD is not associated with a pathological immune response.

  Sleep loss and the inflammatory response to chronic environmental circadian disruption in mice

  BACKGROUND:\nChronic ethanol abuse is associated with disrupted circadian rhythms and sleep. Ethanol administration impairs circadian clock phase-resetting

  suggesting a mode for the disruptive effect of alcohol abuse on circadian timing. Here

  we extend previous studies to explore the effects of chronic forced ethanol on photic phase-resetting

  photic entrainment

  and daily locomotor activity patterns in C57BL/6J mice.\nMETHODS:\nFirst

  microdialysis was used to characterize the circadian patterns of ethanol uptake in the suprachiasmatic (SCN) circadian clock and correlate this with systemic ethanol levels and episodic drinking of 10 or 15% ethanol. Second

  the effects of chronic forced ethanol drinking and withdrawal on photic phase-delays of the circadian activity rhythm were assessed. Third

  the effects of chronic ethanol drinking on entrainment to a weak photic zeitgeber (1 minute of 25 lux intensity light per day) were assessed. This method was used to minimize any masking actions of light that could mask ethanol effects on clock entrainment.\nRESULTS:\nPeak ethanol levels in the SCN and periphery occurred during the dark phase and coincided with the time when light normally induces phase-delays in mice. These delays were dose-dependently inhibited by chronic ethanol and its withdrawal. Chronic ethanol did not impede re-entrainment to a shifted light cycle but affected entrainment under the weak photic zeitgeber and disrupted the daily pattern of locomotor activity.\nCONCLUSIONS:\nThese results confirm that chronic ethanol consumption and withdrawal markedly impair circadian clock photic phase-resetting. Ethanol also disturbs the temporal structure of nighttime locomotor activity and photic entrainment. Collectively

  these results suggest a direct action of ethanol on the SCN clock.

  Chronic ethanol disrupts circadian photic entrainment and daily locomotor activity in the mouse