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Terrence Deak

Anny Gano, Tamara L Doremus-Fitzwater, Terrence Deak
Our work in Sprague Dawley rats has shown rapid alterations in neuroimmune gene expression (RANGE) in the hippocampus and paraventricular nucleus of the hypothalamus (PVN). These manifest as increased interleukin (IL)-6 and IκBα, and suppressed IL-1β and tumor necrosis factor alpha during acute ethanol intoxication. The present studies tested these effects across the lifespan (young adulthood at 2-3 months; senescence at 18 and 24 months), as well as across strain (Fischer 344) and sex. The hippocampus revealed age-dependent shifts in cytokine expression (IL-6, IL-1β, and monocyte chemoattractant protein 1), but no changes were observed in the PVN at baseline or following ethanol...
March 17, 2017: Neurobiology of Aging
Anny Gano, Ricardo Marcos Pautassi, Tamara L Doremus-Fitzwater, Terrence Deak
Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g. interleukins-1 and 6 [IL-1β and IL-6, respectively] and tumor necrosis factor alpha [TNFα])) in several brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus (HPC). It is unknown, however, whether cues associated with ethanol can elicit conditioned alterations in cytokine expression. The present study analyzed, in male Sprague-Dawley rats, whether ethanol-induced changes in the central cytokine response may be amenable to conditioning...
April 2017: Experimental Biology and Medicine
Robert L Spencer, Terrence Deak
Glucocorticoid hormones (cortisol and corticosterone - CORT) are the effector hormones of the hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system. CORT is a systemic intercellular signal whose level predictably varies with time of day and dynamically increases with environmental and psychological stressors. This hormonal signal is utilized by virtually every cell and physiological system of the body to optimize performance according to circadian, environmental and physiological demands. Disturbances in normal HPA axis activity profiles are associated with a wide variety of physiological and mental health disorders...
November 18, 2016: Physiology & Behavior
Michael B Hennessy, Amanda D Schreibeis, Patricia A Schiml, Terrence Deak
Early-life stress is thought to increase later vulnerability for developing depressive illness by sensitizing underlying stress-responsive systems. Guinea pig pups separated from their mother and isolated in a novel cage for 3 hr exhibit a sensitized depressive-like behavioral response when separated again the following day as well as weeks later. The behavioral response and its sensitization appear to be mediated by inflammatory factors. To determine if this sensitization is specific to the separation response or if it reflects a broader underlying depressive-like state, guinea pig pups that had either been separated for 3 hr or remained with their mothers were observed in the forced swim test the following 3 days...
January 2017: Developmental Psychobiology
Anny Gano, Tamara L Doremus-Fitzwater, Terrence Deak
Acute ethanol intoxication is associated with Rapid Alterations in Neuroimmune Gene Expression (RANGE), including increased Interleukin (IL)-6 and Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and suppressed IL-1β and Tumor necrosis factor (TNF) α, yet little is known about adaptations in cytokines across the first few ethanol exposures. Thus, the present studies examined central cytokines during intoxication (3h post-ethanol) following 2, 4 or 6 intragastric ethanol challenges (4g/kg) delivered either daily or every-other-day (EOD)...
September 1, 2016: Brain Research
Anastacia Y Kudinova, Terrence Deak, Cara M Hueston, John E McGeary, Valerie S Knopik, Rohan H C Palmer, Brandon E Gibb
Extensive evidence highlights the role of inflammatory processes in major depressive disorder (MDD). However, most studies have examined a consistent set of inflammatory cytokines and there is evidence that other immune-derived products may play a role in MDD. In this article, we present data from 3 complimentary studies that support the role of a novel cytokine, interleukin-33 (IL-33), in depression risk. First, we show that a 2-SNP haplotype in the IL-33 gene (rs11792633 and rs7044343) moderated the link between women's history of childhood abuse and their history of recurrent MDD (rMDD), such that the link between childhood abuse and rMDD was stronger among women with fewer copies of the protective IL-33 CT haplotype...
2016: Journal of Abnormal Psychology
Amy E Perkins, Tamara L Doremus-Fitzwater, Robert L Spencer, Elena I Varlinskaya, Melissa M Conti, Christopher Bishop, Terrence Deak
Aging results in a natural decline in social behavior, yet little is known about the processes underlying these changes. Engaging in positive social interaction is associated with many health benefits, including reduced stress reactivity, and may serve as a potential buffer against adverse consequences of aging. The goal of these studies was to establish a tractable model for the assessment of social behavior deficits associated with late aging. Thus, in Exp. 1, 1.5-, 3-, and 18-month-old male Fischer 344 (F344) rats were assessed for object investigation, and social interaction with a same-aged partner (novel/familiar), or a different-aged partner, thereby establishing working parameters for studies that followed...
April 2016: Experimental Gerontology
Terrence Deak, Matt Quinn, John A Cidlowski, Nicole C Victoria, Anne Z Murphy, John F Sheridan
The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative or antagonistic interactions between steroid hormone receptors (estrogen and glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan...
2015: Stress: the International Journal on the Biology of Stress
Terrence Deak, Pamela S Hunt
No abstract text is available yet for this article.
September 1, 2015: Physiology & Behavior
Tamara L Doremus-Fitzwater, Anny Gano, Jacqueline E Paniccia, Terrence Deak
Alcohol induces widespread changes in cytokine expression, with recent data from our laboratory having demonstrated that, during acute ethanol intoxication, adult rats exhibit consistent increases in interleukin (IL)-6 mRNA expression in several brain regions, while showing reductions in IL-1 and TNFα expression. Given evidence indicating that adolescence may be an ontogenetic period in which some neuroimmune processes and cells may not yet have fully matured, the purpose of the current experiments was to examine potential age differences in the central cytokine response of adolescent (P31-33days of age) and adult (69-71days of age) rats to either an acute immune (lipopolysaccharide; LPS) or non-immune challenge (ethanol)...
September 1, 2015: Physiology & Behavior
Kelly Bordner, Terrence Deak
BACKGROUND: Despite considerable knowledge that prenatal ethanol exposure can lead to devastating effects on the developing fetus, alcohol consumption by pregnant women remains strikingly prevalent. Both clinical and basic research has suggested that, in addition to possible physical, behavioral, and cognitive deficits, gestational exposure to alcohol may lead to an increased risk for the development of later alcohol-related use and abuse disorders. The current work sought to characterize alterations in endogenous opioid signaling peptides and gene expression produced by ethanol exposure during the last days of gestation...
September 1, 2015: Physiology & Behavior
Michael B Hennessy, Nathan P Stafford, Brittany Yusko-Osborne, Patricia A Schiml, Evan D Xanthos, Terrence Deak
Early life stress can increase susceptibility for later development of depressive illness though a process thought to involve inflammatory mediators. Isolated guinea pig pups exhibit a passive, depressive-like behavioral response and fever that appear mediated by proinflammatory activity, and which sensitize with repeated separations. Treatment with an anti-inflammatory can attenuate the behavioral response during the initial separation and separation the following day. Here we used the cyclooxygenase inhibitor naproxen to examine the role of prostaglandins in mediating the depressive-like behavior and core body temperature of young guinea pigs during an initial separation, separation the next day, and separation 10 days after the first...
February 2015: Physiology & Behavior
Keiko Arakawa, Hiroyuki Arakawa, Cara M Hueston, Terrence Deak
Exposure to stressors such as foot shock (FS) leads to increased expression of multiple inflammatory factors, including the proinflammatory cytokine interleukin-1 (IL-1) in the brain. Studies have indicated that there are sex differences in stress reactivity, suggesting that the fluctuations in gonadal steroid levels across the estrous cycle may play a regulatory role in the stress-induced cytokine expression. The present studies were designed to investigate the role of 17-β-estradiol (E2) and progesterone (Pg) in regulating the cytokine response within the paraventricular nucleus (PVN) of the hypothalamus through analysis of gene expression with real-time RT-PCR...
2014: Neuroendocrinology
Brian Lord, Leah Aluisio, James R Shoblock, Robert A Neff, Elena I Varlinskaya, Marc Ceusters, Timothy W Lovenberg, Nicholas Carruthers, Pascal Bonaventure, Michael A Letavic, Terrence Deak, Wilhelmus Drinkenburg, Anindya Bhattacharya
In the central nervous system, the ATP-gated Purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is expressed in glial cells and modulates neurophysiology via release of gliotransmitters, including the proinflammatory cytokine interleukin (IL)-1β. In this study, we characterized JNJ-42253432 [2-methyl-N-([1-(4-phenylpiperazin-1-yl)cyclohexyl]methyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide] as a centrally permeable (brain-to-plasma ratio of 1), high-affinity P2X7 antagonist with desirable pharmacokinetic and pharmacodynamic properties for in vivo testing in rodents...
December 2014: Journal of Pharmacology and Experimental Therapeutics
Tamara L Doremus-Fitzwater, Hollin M Buck, Kelly Bordner, Laura Richey, Megan E Jones, Terrence Deak
BACKGROUND: Evidence has emerged demonstrating that ethanol (EtOH) influences cytokine expression within the central nervous system, although most studies have examined long-term exposure. Thus, the cytokine response to an acute EtOH challenge was investigated, in order to characterize profiles of cytokine changes following acute exposure. METHODS: Rats pups were injected intraperitoneally (i.p.) with 2-g/kg EtOH, and IL-1 mRNA and protein were assessed 0, 60, 120, 180, and 240 minutes post injection (Experiment 1)...
August 2014: Alcoholism, Clinical and Experimental Research
Joseph M Catanzaro, Cara M Hueston, Molly M Deak, Terrence Deak
Stress leads to neuroinflammatory and behavioral consequences through upregulation of inflammatory-related cytokines within the central nervous system such as interleukin-1β (IL-1β), which may be indicative of microglial priming/activation. Evidence suggests that the P2X7 receptor (P2X7R) may play an important role in the synthesis and conversion of IL-1β. In a series of six experiments, adult male rats were intubated with a highly selective P2X7R antagonist (A-804598) before footshock exposure. As expected, footshock increased IL-1β and CD14 mRNA in the paraventricular nucleus, and A-804598 (25 mg/kg) partially attenuated these effects...
September 2014: Behavioural Pharmacology
Cara M Hueston, Terrence Deak
Although progesterone is most commonly regarded in terms of its role in the female estrous cycle, reproductive behavior, and pregnancy, progesterone is also a precursor to corticosterone (CORT) and is released from the adrenal glands of both sexes in response to stress. However, the relationship between plasma CORT and progesterone during times of stress has not been well established. To better characterize dynamic changes in progesterone release as a result of stressor exposure, plasma progesterone levels were measured using enzyme immunoassay under multiple conditions, including after stress exposure (footshock, restraint, and forced swim), manipulations of the hypothalamic-pituitary-adrenal axis (injection of metyrapone or dexamethasone, or adrenalectomy), and in response to CRH and ACTH injections...
September 2014: Endocrinology
Cara M Hueston, Terrence Deak
Acute stress increases the expression of cytokines and other inflammatory-related factors in the CNS, plasma, and endocrine glands, and activation of inflammatory signaling pathways within the hypothalamic-pituitary-adrenal (HPA) axis may play a key role in later stress sensitization. In addition to providing a summary of stress effects on neuroimmune changes within the CNS, we present a series of experiments that characterize stress effects on members of the interleukin-1β (IL-1) super-family and other inflammatory-related genes in key structures comprising the HPA axis (PVN, pituitary and adrenal glands), followed by a series of experiments examining the impact of exogenous hormone administration (CRH and ACTH) and dexamethasone on the expression of inflammatory-related genes in adult male Sprague-Dawley rats...
January 30, 2014: Physiology & Behavior
Michael B Hennessy, Terrence Deak, Patricia A Schiml
During pathogen exposure or some forms of stress, proinflammatory processes induce an array of motivated and behavioral adjustments termed "sickness behaviors". Although withdrawal from social interactions is a commonly observed sickness behavior, the relation between social behavior and sickness is much more complex. Sickness can suppress or stimulate social behavior. Sickness can serve as a social cue. Stressors that are social in nature can induce sickness behaviors, and sickness behavior can be readily suppressed by meaningful social stimuli...
March 2014: Brain, Behavior, and Immunity
Peter Blandino, Cara M Hueston, Christopher J Barnum, Christopher Bishop, Terrence Deak
The impact of acute stress on inflammatory signaling within the central nervous system is of interest because these factors influence neuroendocrine function both directly and indirectly. Exposure to certain stressors increases expression of the proinflammatory cytokine, Il-1β in the hypothalamus. Increased IL-1 is reciprocally regulated by norepinephrine (stimulatory) and corticosterone (inhibitory), yet neural pathways underlying increased IL-1 have not been clarified. These experiments explored the impact of bilateral lesions of the ventral noradrenergic bundle (VNAB) on IL-1 expression in the paraventricular nucleus of the hypothalamus (PVN) after foot shock...
July 2013: Endocrinology
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