Browsing by Author "Hickman, Debra"

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    Glucocorticoid Induced Leucine Zipper in Lipopolysaccharide Induced Neuroinflammation
    (Frontiers, 2019) Witek, Emily; Hickman, Debra; Lahiri, Debomoy K.; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of Dentistry
    Glucocorticoids (GC) are steroid hormones secreted as the end-product of the neuroendocrine stress cascade. Both absence and elevated GC mediate neurotoxic responses, suggesting that a narrow window ranging from physiological to slightly high GC mediate protective responses. The beneficial effects of GC are attributed to the transactivation of regulatory proteins and inhibition mediated by glucocorticoid receptor interactions with other co-factors. The glucocorticoid induced leucine zipper (GILZ) is a gene strongly upregulated by GC and mediates many of the anti-inflammatory and anti-proliferative effects of GC. Although GILZ is constitutively expressed in many tissues including the brain, the expression has been shown to occur with varying dynamics suggesting that the local milieu modulates its expression with consequent effects on cellular responses. Here we investigated the expression profile of GILZ in lipopolysaccharide mediated neuroinflammation model of Alzheimer’s disease. Our data suggest that the GILZ expression is downregulated in neuroinflammation correlating inversely with the pro-inflammatory cytokines and innate immune responses.
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    Glucocorticoid Induced Leucine Zipper in Lipopolysaccharide Induced Neuroinflammation
    (Frontiers, 2019-01-25) Witek, Emily; Hickman, Debra; Lahiri, Debomoy K.; Srinivasan, Mythily; Psychiatry, School of Medicine
    Glucocorticoids (GCs) are steroid hormones secreted as the end-product of the neuroendocrine stress cascade. Both absence and elevated GC mediate neurotoxic responses, suggesting that a narrow window ranging from physiological to slightly high GC mediate protective responses. The beneficial effects of GC are attributed to the transactivation of regulatory proteins and inhibition mediated by glucocorticoid receptor (GR) interactions with other co-factors. The glucocorticoid induced leucine zipper (GILZ) is a gene strongly upregulated by GC and mediates many of the anti-inflammatory and anti-proliferative effects of GC. Although GILZ is constitutively expressed in many tissues including the brain, the expression has been shown to occur with varying dynamics suggesting that the local milieu modulates its expression with consequent effects on cellular responses. Here we investigated the expression profile of GILZ in lipopolysaccharide (LPS) mediated neuroinflammation model of Alzheimer’s disease (AD). Our data suggest that the GILZ expression is downregulated in neuroinflammation correlating inversely with the pro-inflammatory cytokines and innate immune responses.
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    Isoflurane and Carbon Dioxide Elicit Similar Behavioral Responses in Rats
    (MDPI, 2020-08-16) Kulkarni, Satyajit; Hickman, Debra; Laboratory Animal Resource Center, IU School of Medicine
    Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to expand upon previously published work evaluating the aversiveness of CO2 by introducing an isoflurane treatment group in parallel. Aversion was tested using a forced exposure setup and an aversion-avoidance setup. In the first part of the study, 12 naïve female Sprague–Dawley rats were exposed during four consecutive days, once to each of four treatments: isoflurane, fox urine, oxygen, and CO2. In the second part of the study, 24 naïve female Sprague–Dawley rats and 12 rats from the first experiment were exposed to CO2, isoflurane, or both gases. In the forced exposure study, there were no significant differences between CO2 and isoflurane treatments except in line crosses. Overall, rats were more active in the isoflurane and CO2 treatments compared to the control groups, suggesting that isoflurane and CO2 are similarly aversive. In the aversion-avoidance study, rats previously exposed to isoflurane left the dark chamber significantly earlier compared to naïve rats during exposure to isoflurane. We also show that learned aversion to isoflurane is sustained for at least 15 days after initial exposure. Given this result, we suggest that CO2 is superior to isoflurane when euthanizing rodents with prior exposure to isoflurane. Overall, these results confirm previous studies which suggest that care should be taken when considering the serial use of isoflurane as an anesthetic.
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    Nuclear factor-kappa B: Glucocorticoid-induced leucine zipper interface analogs suppress pathology in an Alzheimer's disease model
    (Elsevier, 2018-01-01) Srinivasan, Mythily; Lahiri, Niloy; Thyagarajan, Anish; Witek, Emily; Hickman, Debra; Lahiri, Debomoy K.; Oral Pathology, Medicine and Radiology, School of Dentistry
    Introduction Glucocorticoid-induced leucine zipper is a regulatory protein that sequesters activated nuclear factor-kappa B p65. Previously, we showed that rationally designed analogs of the p65-binding domain of glucocorticoid-induced leucine zipper, referred to as glucocorticoid-induced leucine zipper analogs (GAs), inhibited amyloid β–induced metabolic activity and inflammatory cytokines in mixed brain cell cultures. Here, we investigate the therapeutic efficacy of GA in an Alzheimer's disease model. Methods GA and control peptides were synthesized covalently as peptide amides with the cell-penetrating agent. C57Bl/6J mice induced with lipopolysaccharide-mediated neuroinflammation (250 mg/kg i.p/day for six days) were treated on alternate days with GA-1, GA-2, or control peptides (25 mg/kg i.v). Brain tissues were assessed for gliosis, cytokines, and antiapoptotic factors. Results The brain tissues of GA-1– and GA-2–treated mice exhibited significantly reduced gliosis, suppressed inflammatory cytokines, and elevated antiapoptotic factors. Discussion The antineuroinflammatory effects of GA suggest potential therapeutic application for Alzheimer's disease.
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    Predictive Value of Grooming Behavior for Development of Dermatitis in Selectively Bred P Rats as a Model of Trichotillomania Hair Pulling Disorder
    (MDPI, 2022-02-18) Hickman, Debra; Prakash, Anjali; Bell, Richard; Psychiatry, School of Medicine
    Trichotillomania (TTM) is a body-focused repetitive disorder affecting as much as 0.5 to 2% of the population, with women four times more likely to be affected than men. This disorder causes impairment in daily function and significant distress. A potential animal model for this disorder is the inbred C57BL/6J mouse which displays clinical signs and behavioral characteristics similar to those described for people affected by this disorder. Because alcohol-preferring P rats also display similar clinical signs and behavioral characteristics, it was hypothesized that this selectively bred stock could be an additional animal model. In this study, 112 female P rats were recorded on digital media for 15 min after being sprayed with a mist of water and assessed for grooming patterns—oral, manual, and scratching. Significant elevations in scratching and oral grooming behavior were predictive of the future development of skin lesions. These findings suggest that P rats may be an additional model to study TTM, with the advantage of increased genetic variation (i.e., non-inbred) which mirrors the human population. The use of this model may help to identify preventative and therapeutic interventions for humans and other animals with similar body-focused repetitive disorders.
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    The Future Is Not Bright: Evaluation of Rat Preferences for Color and Intensity of Light
    (MDPI, 2024-07-12) Swan, Melissa; Horvath, Aidan; Pritchett, Rebecca K.; Barabas, Amanda J.; Hickman, Debra; Gaskill, Brianna N.; Laboratory Animal Resource Center, School of Medicine
    Light is a key factor influencing the welfare of laboratory rodents, but little is known about their optimal lighting condition. It i common knowledge that rats prefer dim light, so bright light is mitigated with red-tinted shelters or cages, which alter both the color and intensity of light. Because both aspects are altered, the contribution of each feature to rodent preference is unknown. Further, it is unknown if this preference is influenced by previous experience. We hypothesized that rats would prefer lower light intensity and that their preferences would be influenced by their housing environment. Breeder pairs of rats were randomly separated into four treatments groups: red 200 lux, red 25 lux, clear 200 lux, and clear 25 lux. The breeders' offspring were tested three times in an apparatus that offered access to each environment, and their preferences were analyzed. Generally, the rats preferred the lower-lux environments and showed no color preference. However, the rats from the clear, 200 lux cages, preferred clear caging and only showed a preference for 25 lux conditions during the second and third preference tests. These results suggest that the light intensity, more than color, should be considered when designing rodent housing and testing facilities.