Dr. Karen Scott Research Profile

Contributions to Science

  1. After completing MS in Animal Sciences and working for the USDA-ARS Livestock Behavior Research Unit as a staff scientist, Dr. Scott joined the laboratory of Dr. Timothy H. Moran at Johns Hopkins University as a laboratory technician and laboratory manager.  It was during this period that she realized that she could combine her interests in the neural control of food intake and regulation of body weight with her background in stress physiology, and this motivated her to pursue a doctorate in Neuroscience.  While at Johns Hopkins, Dr. Scott learned surgical, behavioral, and analytical techniques for investigating neural control of food intake and body weight. Dr. Scott also published and presented data at national and international conferences. During this time, her group determined that exendin-4, a glucagon-like peptide 1 (GLP-1) receptor agonist, reduces food intake in nonhuman primates via reductions in the size of meals, rather than the number, suggesting that at lower doses it induces satiety, rather than malaise. Dr. Scott also conducted several studies focusing on the role of the compact region of the dorsomedial hypothalamic nucleus in the metabolism of rodents. Voluntary exercise results in short-term reductions in body weight and food intake of rodents, and her group demonstrated that these effects are a result of reductions in meal size, mediated in part by corticotropin-releasing factor (CRF) within the DMH.  They also demonstrated, through viral-mediated overexpression and silencing, that neuropeptide Y (NPY) within this region plays a critical role in body weight regulation and that increased NPY expression within the DMH facilitates the development of obesity.
    1. Kawaguchi M, Scott KA, Moran TH, Bi S (2005) Dorsomedial hypothalamic corticotropin-releasing factor mediation of exercise-induced anorexia. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 288:1800-1805
    2. Scott KA, Moran TH (2007) The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 293: R983-987.
    3. Yang L*, Scott KA*, Hyun J, Tamashiro KL, Tray N, Moran TH, Bi S (2009) Role of dorsomedial hypothalamic neuropeptide Y in modulating food intake and energy balance. Journal of Neuroscience 29:179-190. (*Authors contributed equally to this work)
    4. Smedh U, Scott KA, Moran TH (2015) Fourth ventricular CART peptide induces c-fos in the area postrema and nucleus of the solitary tract via a CRF-receptor dependent mechanism. Neuroscience Letters 609:124-8.

 

During her  Ph.D. Dr. Scott focused on early life experience and its effects on adult physiology and behavior. She investigated the effects of in vitro manipulations commonly utilized in assisted reproductive technologies (in vitro fertilization, IVF, and intracytoplasmic sperm injection, ICSI) as well as somatic cell nuclear transfer (SCNT) on body weight and glucose metabolism. Her group found that mice exposed to in vitro manipulation following IVF, ICSI and SCNT techniques exhibit alterations in birth weight and glucose tolerance and/or insulin levels in response to glucose bolus as young adults. Interestingly, some of these effects are sex-specific, and appear to develop prior to an obese phenotype.  The focus of my dissertation work and pre-doctoral NRSA, was the effects of prenatal psychological stress exposure on neuroendocrine responses to stress and social hierarchy formation in male rats.  Male rats exposed to chronic variable stress during the last week of gestation were significantly more likely to become subordinate when housed in a naturalistic burrow system in adulthood.  However, instead of exhibiting an exacerbation of the weight loss and elevations in corticosterone that is normally observed in subordinate males, they appeared more resilient to stress, exhibiting little to no weight loss and no elevation in basal corticosterone levels. While at University of Cincinnati, Dr. Scott also participated in multiple projects investigating the interrelationships between the RAAS and HPA axis in response to acute and chronic stress exposure with and without pharmacological and/or dietary manipulations.

    1. Scott KA, Yamazaki Y, Yamamoto M, Lin Y, Melhorn SJ, Krause EG, Woods SC, Yanagimachi R, Sakai RR, Tamashiro KLK (2010) Glucose parameters are altered in mouse offspring produced by assisted reproductive technologies and somatic cell nuclear transfer. Biology of Reproduction 83:220-227.
    2. Scott KA, Tamashiro KLK, Sakai RR (2012) Chronic social stress: Effects on neuroendocrine function. In: Fink G, Pfaff DW, Levine JE, eds. Handbook of Neuroendocrinology. London, Waltham, San Diego: Academic press, Elsevier 521-534.Scott KA, Melhorn SJ, Sakai RR (2012) Effects of chronic social stress on obesity. Current Obesity Reports 1:16-25.
    3. Smeltzer MD, Scott KA, Melhorn SJ, Krause EG, Sakai RR (2012) Amylin blunts hyperphagia and reduces weight and fat gain during recovery in socially stressed rats. American Journal of Physiology – Regulatory Integrative and Comparative Physiology 303: R676-682.
    4. Scott KA, de Kloet AD, Smeltzer MD, Krause EG, Flak JN, Melhorn SJ, Foster MT, Tamashiro KLK, Sakai RR (2017) Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status. Physiology & Behavior 178: 117-125.

 

Her  postdoctoral training built upon her background in behavioral neuroendocrinology and her interests in metabolic and mood disorders. dr. Scott began her postdoctoral training with a project looking at the potential use of microRNAS (miRNAs) as biomarkers for diagnosis and/or prediction of treatment response in patients with treatment-resistant depression (TRD), and found that expression of 2 miRNAs, let-7b and let-7c, were lower in whole blood samples from patients with treatment-resistant depression. However, these did not change following treatment by ECT or ketamine, and were not predictive of treatment response. Dr. Scott then headed a project at the APC microbiome institute finding that aging in male mice is associated with cognitive impairments that are correlated with elevations in peripheral inflammation, impaired gut barrier function, and changes in gut microbiota. Furthermore, some of these effects, including cognitive dysfunction are partially attenuated through dietary manipulations.

    1. Scott KA, Hoban AE, Clarke G, Moloney GM, Dinan TG, Cryan JF (2015) Thinking small: towards microRNA-based therapeutics for anxiety disorders. Expert Opinion on Investigational Drugs 24:529-542.
    2. Gururajan A*, Naughton ME*, Scott KA*, O’Connor RM, Moloney G, Clarke G, Dowling J, Walsh A, Ismail F, Shorten G, Scott L, McLoughlin DM, Cryan JF, Dinan TG (2016) MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c. Translational Psychiatry 6: e862. (*Authors contributed equally to this work)
    3. Scott KA, Ida M, Peterson VL, Prenderville JA, Moloney GM, Izumo T, Murphy K, Murphy A, Ross RP, Stanton C, Dinan TG, Cryan JF (2017) Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse. Brain, Behavior, and Immunology 65: 20-32.
    4. Boehme M, van de Wouw M, Bastiaanssen TFS, Olavarría-Ramírez L, Lyons K, Fouhy F, Golubeva AV, Moloney GM, Minuto C, Sandhu KV, Scott KA, Clarke G, Stanton C, Dinan TG, Schellekens H, Cryan JF (2020) Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome. Molecular Psychiatry 25(10):2567-2583.

 

Since joining the Krause/de Kloet lab, Dr. Scott has continued to focus on the bidirectional communication between the brain and the periphery and how manipulations of the RAAS and oxytocinergic system affect behavior and physiology. Over the past 2 years, she has utilized different mouse genetic lines and several techniques including Opto- and chemo-genetics, in vivo calcium imaging, indirect calorimetry, and radiotelemetry in the Krause and de Kloet labs. These techniques, in conjunction with a variety of neuroanatomical, molecular, and methods uniquely position the lab to investigate the complex relationship between brain and periphery, and the critical role of oxytocin in both behavior and interoception.

    1. de Kloet AD, Cahill KM, Scott KA, Krause EG (2020) Overexpression of angiotensin-converting enzyme 2 reduces anxiety-like behavior in female mice. Physiology and Behavior 224:113002.

Frazier CJ, Harden SW, Alleyne AA, Mohammed M, Sheng W, Smith JA, Elsaafien K, Spector EA, Johnson DN, Scott KA, Krause EG, de Kloet AD (2020) An angiotensin-responsive connection from the lamina terminalis to the paraventricular nucleus of the hypothalamus evokes vasopressin secretion to increase blood pressure in mice. Journal of Neuroscience https://doi.org/10.1523/JNEUROSCI.1600-20.2020