GSBSE student Cong Tian Publishes in PLOS ONE, Human Molecular Genetics, and Aging

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis
Authors: Cong Tian, Belinda S Harris, Kenneth R Johnson
Publication date: 2016/12/13
Journal: PloS one

The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells
Authors: Junhuang Zou, Qian Chen, Ali Almishaal, Pranav Dinesh Mathur, Tihua Zheng, Cong Tian, Qing Y Zheng, Jun Yang
Publication date: 2016/12/28
Journal: Human Molecular Genetics

N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in γ-glutamyl transferase 1 deficient mice.
Authors: Dalian Ding, Haiyan Jiang, Guang-Di Chen, Chantal Longo-Guess, VP Muthaiah, Cong Tian, Adam Sheppard, Richard Salvi, Kenneth R Johnson
Publication date: 2016/4
Journal: Aging

GSBSE Student Emily Spaulding publishes mini-review in Frontiers in Neuroscience

The specialized structure of the neuron requires that homeostasis is sustained over the meter or more that may separate a cell body from its axonal terminus. Given this impressive distance and an axonal volume that is many times that of the cell body, how is such a compartment grown during development, re-grown after injury, and maintained throughout adulthood? While early answers to these questions focused on the local environment or the cell soma as supplying the needs of the axon, it is now well-established that the axon has some unique needs that can only be met from within. Decades of research have revealed local translation as an indispensable mechanism of axonal homeostasis during development and regeneration in both invertebrates and vertebrates. In contrast, the extent to which the adult, mammalian axonal proteome is maintained through local translation remains unclear and controversial. This mini-review aims to highlight important experiments that have helped to shape the field of axonal translation, to discuss conceptual arguments and recent evidence that supports local translation as important to the maintenance of adult axons, and to suggest experimental approaches that have the potential to further illuminate the role of axonal translation in neuronal homeostasis.

Accumulating Evidence for Axonal Translation in Neuronal Homeostasis.
Spaulding EL, Burgess RW.
Front Neurosci . 2017 May 31;11:312. doi: 10.3389/fnins.2017.00312. eCollection 2017. Review.
PMID: 28620277

Alumnus Seungbum Choi awarded grant from the Korean Research Foundation

Dr. Choi, a research assistant professor at Cachon Cardiovascular Research Institute, was awarded $150,000 from the Korean Research Foundation to investigate the development of biomarkers and novel therapeutic options for pulmonary arterial hypertension.

GSBSE Faculty publishes on the “Jolly Fat Hypothesis”

Previous cross-sectional research with older adults in the 1970’s led to the conclusion that being overweight as measured by body mass index (BMI) was related to lower levels of depressive symptoms. This phenomenon came to be known as the “jolly fat hypothesis.”  The hypothesis was that higher BMI might be protective against symptoms of depression, possibly by reducing risk of frailty.

However, the studies supporting the jolly fat hypotheses have been cross sectional (performed at a single point in time) and thus it has been impossible to answer several important questions:  Does BMI predict symptoms of depression; do symptoms of depression predict BMI; or are both pathways predictive over time?

Members of the Maine-Syracuse Longitudinal Study research team, led by psychology graduate student Peter Dearborn, employed the MSLS database and a longitudinal design to answer the questions regarding directionality of the jolly fat phenomenon.  Some studies since the 1970s have shown that obesity may be related to higher, not lower, symptoms of depression. However, these results were obtained particularly among younger adults and the relationship between BMI and symptoms of depression among older adults remained less clear. The MSLS is uniquely situated to address this issue. This study of community-dwelling older (n = 638, ages ≥ 50y) adults in the Central New York area was conducted as part of the larger 35-year Maine-Syracuse Longitudinal Study.  

Peter J Dearborn, Michael A Robbins, and Merrill F (Pete) Elias examined the bidirectional relationships between symptoms of depression and BMI over a period of five years using objective measures of BMI and physical functioning.  They examined both pathways simultaneously because there is research indicating that pathways in both directions may be predictive. In the study, we adjusted for baseline BMI and depressive symptoms as well as demographic variables (age, sex, education, marital status), social variables (social activity, social isolation, recent life events), and physical health variables (chronic health conditions, ability to complete 3 timed performance tasks). 

The MSLS investigators found that, although participants underestimated their weight and overestimated their height (producing very different obesity rates 29.2% vs. 38.8%), self-reported BMI and objectively measured BMI related quite similarly to symptoms of depression.  Specifically, higher BMI was related to increases in depressive symptoms over a 5-year period. Interestingly, we did not find the reverse relationship of high levels of depressive symptoms predicting increases in BMI.
As in many previous studies, women reported higher levels of depressive symptoms compared with men, but the risks associated with BMI functioned similarly among both sexes.  

The results of our study indicate that, as is true for younger adults, older adults with higher BMI are at a risk for developing depressive symptoms over time.  Being overweight does not protect against symptoms of depression in elder persons. It is possible that increased weight-stigmatization over the last 20 years has led to older adults “catching up” with younger adults with respect to BMI-associated risk for depressive symptoms.  This may explain why our study found the reverse of predictions based on the jolly fat hypothesis.  Interestingly additional findings from the analysis indicate that increasing physical function through maintenance of physical activity may be a protective factor in the development of depressive symptoms and that this is true independent of any relationship with weight loss or weigh status.

Link to full article: http://digitalcommons.library.umaine.edu/cgi/viewcontent.cgi?article=1015&context=longitudinal_papers

Peter Dearborn is a senior graduate student in the Department of Psychology, Merrill F. (Pete) Elias, and Michael A. Robbins are faculty members in the Department and cooperating faculty in the Graduate School of Biomedical Science and Engineering.

GSBSE Faculty Merrill Elias publishes on Hypertension

Two invited peer review editorials published by Merrill F. Elias and colleagues in May and June, were motivated by two important current themes in the treatment of high blood pressure: (1) intensive lowering of blood pressure to a new goal for management of arterial hypertension; (2) delayed response (lowering of BP to traditional levels) results in increased risk for cardiovascular disease, cerebral-vascular disease and death. The articles are:

 Elias MF, Torres RV, Davey A. Intensive blood pressure control improves cognitive performance: pushing the envelope cum judicia. Am J Hypertens. 2017;30:556–558. doi: 10.1093/ajh/hpx043.

 Elias, M. F & Torres, R. V. Delayed response to antihypertensive medication: a harbinger of stroke, heart failure, and vascular disease. Hypertension; 2017: DOI: 10.1161/HYPERTENSIONAHA.117.09306.

The first paper published in the American Journal of Hypertension is in response to a paper in the same journal indicating the benefits to cognitive performance of lowering BP levels from the traditional 140/90 mmHg to a more intensive treatment standard of 120 mmHg for systolic pressure (the top number). The authors comment that further lowering of blood pressure to this intensive control level is not without risk of adverse side effects in some individuals and that this goal needs to be pursued with maximum information about the patients’ histories as thorough histories might be predictive of side effects.

 The second editorial was in response to a paper in the same issue of Hypertension presenting data indicating that a delayed response to treatment, even if ultimately controlled, was related to adverse cardiovascular disease outcomes including stroke. Elias and Torres review a number of proposed reasons to account for the delayed response to treatment in some individuals, e.g. genetic differences in response to treatment, and a “one size fits all” approach that often fails to tailor the selection of drugs to the mechanisms underlying various types of hypertension.

This personalized approach to treatment is more costly than structured step-care approaches but the cost of diagnosis has to be weighed against the cost of treating cardiovascular and cerebrovascular consequences of delayed response to treatment or complete failure to lower blood pressure.

 Merrill F. (Pete Elias) is Professor of Psychology and Cooperating Professor in the Graduate School of Biomedical Sciences and Engineering, University of Maine. Rachael A. Torres, a graduate of the Psychology Department at the University of Maine, is currently a graduate student in the Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware. Adam Davey is Professor of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware and Vice President for Research, Starr Laboratory, University of Delaware. All authors are members of the Maine-Syracuse Longitudinal Study research team, University of Maine.

GSBSE Student Joshua Havelin Presented at the Annual American Pain Society Meeting

Josh presented at the annual APS (American Pain Society) meeting in Pittsburgh, in the form of a “data-blitz”, 5-minutes of presentation and 5-minutes of questions.  His talk was titled “Mechanistic Distinctions Between Cancer-Induced Ongoing Pain and Movement-Triggered Breakthrough Pain”

Link:  http://americanpainsociety.org/annual-meeting/2017/data-blitz

Alumna Megan Beauchemin presents poster on Acute treatment with the antipsychotic drug, risperidone, alters brain activity and circadian rhythms in the heart.

Karen Houseknecht’s lab (UNECOM) participated in the annual Costas T. Lambrew Maine Medical Center Research Retreat on May 2, 2017 held at Maine Medical Center in Portland.  Work from Karen’s lab which focuses on the regulation of mood and metabolism and specifically the role of psychiatric medications in modulating metabolic status, was highlighted in 2 poster presentations. 

Megan Beauchemin, PhD, Post-doctoral fellow in the laboratory, presented a poster entitled: “Acute treatment with the antipsychotic drug, risperidone, alters brain activity and circadian rhythms in the heart”.  This poster was awarded the 2nd place award in the Basic Science category for scientific presentations.  This work shows for the first time that antipsychotic medications activate areas in the brain associated with regulation of circadian function and also alter the expression of circadian genes in the heart.  Houseknecht, senior author on the work, proposes that these data suggest that antipsychotic medications, which are widely prescribed off-label to vulnerable populations including children, may cause early effects on cardiac function that have been previously undetected.

Collaborators on this work include Dr. Katie Motyl and Dr. Anyonya Guntar, Department of Molecular Medicine, Maine Medical Center Research Institute; Deborah Barlow (technician, Houseknecht lab); Celeste Bouchard (UNECOM class of 2020) and Peter Cardonna, UNE Imaging Core.

Alumna Anna Sitarski awarded the Thomas Maciag Award for Excellence in Basic and Translational Science

Anna received the award as part of Maine Medical Center Retreat on May 3. She was one of seven speakers invited based on abstracts from the entire MMC research system who submitted. 

King laboratory publishes research article on cancer-induced bone pain

Tamara King, Ph.D., associate professor for the College of Osteopathic Medicine published an original research paper in the peer reviewed journal of the Society for Neurosciences, The Journal of Neuroscience. The paper, entitled “Mediation of movement-induced breakthrough cancer pain by IB4 binding nociceptors in rat”. Patients with primary and metastatic cancer associated bone pain report persistent ongoing pain that is treated with opioids. In addition, many patients develop breakthrough pain, a transient period of severe pain, often triggered by movement, that occurs even when the background ongoing pain is controlled with opioids such as morphine. Notably, treatment of breakthrough pain is currently addition of opioids leading to very large doses of opioids along with severe side effects. A better understanding of these aspects of cancer bone pain is necessary for development of improved treatments of cancer pain. This paper presented a novel preclinical measure of movement-induced breakthrough pain that is observed in the presence of morphine controlling ongoing pain. This allows for examination of mechanisms that underlie cancer-induced breakthrough pain to guide development of improved therapies designed to improve these patient’s quality of life and diminish adverse side effects associated with the current treatments. Along these lines, this research examined the hypotheses that ongoing pain and breakthrough pain are dependent on different subpopulations of sensory fibers from the tumor-bearing limb. The research demonstrated that movement induces a pain state that is observed in the setting of morphine that blocks ongoing pain, mirroring the clinical observations of breakthrough pain. Mechanistic analyses of sensory neurons innervating the tumor bearing hindlimb demonstrated that blockade of sensory input prevents BTP. More specific analysis of sensory input demonstrated that ablation of a certain subset of pain sensory fibers that bind isolectin B4 (IB4)-binding fibers, prevented movement-induced breakthrough pain. In contrast, blocking input from a different set of pain sensory fibers failed to prevent movement induced breakthrough pain. This provides important new information that can be used to explore novel biological targets that may show improved pain relief for episodes of breakthrough pain in cancer patients with skeletal metastases.

 A significant portion of this research was performed by UNE students working in Dr. King’s laboratory. The lead author, Joshua Havelin (UNE Class of 2011) is currently a graduate student in the Graduate School of Biomedical Sciences and Engineering Program and works in Dr. King’s laboratory at UNE. Ian Imbert (2012) obtained a master of public health degree (MPH) while working on this project in Dr. King’s laboratory and now works for Dr. Dora Mills. Ian Pelletier (2015) worked in Dr. King’s laboratory as an undergraduate at UNE as a double major in the departments of chemistry and biology within the college of arts and sciences (CAS). Ian Pelletier is currently a second year student in the college of osteopathic medicine (COM). Jonathon Gentry a senior undergraduate in the department of medical biology within CAS and will be graduating in May of 2017.

Citation: Joshua Havelin, Ian Imbert, Devki Sukhtankar, Bethany Remeniuk, Ian Pelletier, Jonathan Gentry, Alec Okun, Timothy Tiutan, Frank Porreca, Tamara King. “Mediation of movement-induced breakthrough cancer pain by IB4 binding nociceptors in rats”. Journal of Neuroscience. 24 April 2017, 1212-16; DOI: 10.1523/JNEUROSCI.1212-16.2017

Read the full paper.

GSBSE Alumna Ginny McLane featured in 2017 Rising Tide

The “Rising Tide” a publication of the Office of Research and Scholarship at the University of New England has featured Ginny McLane in their 2017 issue.

Ginny completed her PhD in May of 2016 under the guidance of Ling Cao, Ph.D., associate professor in the Department of Biomedical Sciences, College of Osteopathic Medicine at the University of New England.

http://www.une.edu/sites/default/files/Research%26Scolarship_RisingTide2017_021517_Approved_LR.pdf, see page 46.