This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mental health is the expectable endpoint of brain maturation. Recent work shows that early-life rapid eye-movement sleep deprivation (ELRD) has long-lasting effects on synaptic plasticity mechanisms underlying CNS maturation, e.g., extending critical periods for brain development, in part, by altering expression of several neuronal signaling proteins. Other data implicate sleep in the etiology of major depressive disorder (MDD). The rhythmic organization of the sleep electroencelopgraph (EEG), slow-wave EEG activity (SWA), sleep homeostasis, rapid eye-movement (REM) sleep, and the circadian timing of the REM/non-REM (NREM) sleep cycle are all abnormal in early onset MDD. Similar findings have been reported for children at high risk for depression on the basis of maternal family history of MDD. These sleep abnormalities likely reflect an increased biological vulnerability to developing MDD in later adolescence. Moreover, there is now good evidence that such sleep abnormalities are sex-dependent, with greater biological rhythm disturbances in depressed women and greater sleep-homeostatic impairment in depressed men. In this project we will examine whether there are critical periods of brain development during which sleep disturbance impacts the risk for MDD. We will employ an established rat model, focusing on the permanence of ELRD effects upon brain maturation. We hypothesize that ELRD predisposes animals to exhibit measurable CNS signs as adults, which are proxies for the symptoms of MDD (1). A primary goal of this work is to determine whether there is a sex bias in the CNS consequences of ELRD. To uncover a likely biological basis for SWA and EEG alterations, we will investigate brain maturation in older adolescent rats after they have experienced ELRD at either of two points (early and late) during perinatal development, or at one (control) time-point during early adolescence. Once these rats reach late adolescence, we will determine functional changes in hippocampal synaptic plasticity as well as neurochemical changes in both hippocampus and prefrontal cortex. Changes in protein levels of serotonergic (5-HT) receptor subtype, 5-HT1A, and the serotonin transporter have been reported in postmortem studies of these same brain areas in depressed humans. It is notable that many antidepressant drugs, including those that reduce serotonin reuptake (SSRIs) also reduce REM sleep, and, when given during developmental periods, induce alterations in the serotonin transporter- and 5-HT1A autoreceptor-function, which are thought to be dysregulated in MDD. In addition, little is known about how ELRD affects developmental plasticity and serotonin receptor regulation in females. Results from the planned studies potentially offer direction in designing drug intervention strategies and development of treatment practices that may improve response to and clinical course of the illness.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017701-10
Application #
8360511
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-07-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$32,102
Indirect Cost
Name
University of Mississippi Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Stoppelbein, Laura; McRae, Elizabeth; Greening, Leilani (2017) A Longitudinal Study of Hardiness as a Buffer for Posttraumatic Stress Symptoms in Mothers of Children with Cancer. Clin Pract Pediatr Psychol 5:149-160
Greening, Leilani; Stoppelbein, Laura; Cheek, Kara (2017) Racial/ethnic disparities in the risk of posttraumatic stress disorder symptoms among mothers of children diagnosed with cancer and Type-1 diabetes mellitus. Psychol Trauma 9:325-333
Ginley, Meredith K; Bagge, Courtney L (2017) Psychiatric heterogeneity of recent suicide attempters: A latent class analysis. Psychiatry Res 251:1-7
Duncan, Jeremy W; Zhang, Xiao; Wang, Niping et al. (2016) Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury. Neuropharmacology 105:329-340
Stewart, Courtney; Yu, Yue; Huang, Jun et al. (2016) Effects of high intensity noise on the vestibular system in rats. Hear Res 335:118-127
Dalwadi, Dhwanil A; Kim, Seongcheol; Amdani, Shahnawaz M et al. (2016) Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz. Pharmacol Res 110:10-24
Fisher, Lauren B; Overholser, James C; Dieter, Lesa (2015) Methods of committing suicide among 2,347 people in Ohio. Death Stud 39:39-43
Stoppelbein, Laura; Greening, Leilani (2015) A longitudinal study of the role of cortisol in posttraumatic stress disorder symptom clusters. Anxiety Stress Coping 28:17-30
Duncan, Jeremy; Wang, Niping; Zhang, Xiao et al. (2015) Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain. Neurotox Res 28:18-31
Johnson, Shakevia; Duncan, Jeremy; Hussain, Syed A et al. (2015) The IFN?-PKR pathway in the prefrontal cortex reactions to chronic excessive alcohol use. Alcohol Clin Exp Res 39:476-84

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