This page is an archive of Centre for Neuroendocrinology new stories from June 2016, back to June 2014.
CNE investigators awarded 4 HRC project grants in 2015/16 round
Left to right: Dr Richard Piet (PI & AI), Professor Allan Herbison (PI), Dr Rebecca Campbell (AI), Dr Karl Iremonger (AI), Assoc. Professor Greg Anderson (PI), Dr Alex Tups (AI), Professor Dave Grattan (PI).
HRC Project grants
Targeting the RFRP neuronal system to control stress and anxiety
Associate Professor Greg Anderson (Anatomy)
Hyperactivity of the stress axis is thought to be one of the fundamental underlying drivers of psychiatric conditions such as generalised anxiety and depression. This has led us and others to develop pharmacological approaches to modify neural stress pathways in the brain. Along these lines, we have recently discovered that the neuropeptide RFRP-3 induces anxious behaviour and enhances acute stress responses in mice. Remarkably, blockade of its receptor with a novel antagonist called GJ14 overcomes these responses. Using powerful new transgenic mouse lines and single cellular through to in vivo behavioural measurements, we will evaluate the role of RFRP-3 on activity of the cells controlling the stress axis, stress hormone secretion and various anxiety-related behaviours. We will then develop and evaluate new RFRP-3 receptor antagonists with improved ability to enter the brain following oral delivery, potentially opening an entirely new avenue for treating stress and anxiety related disorders.
Other Otago Named Investigators: Dr Karl Iremonger, Associate Professor Joel Tyndall, Dr Andrea Vernall
Role of hypothalamic beta-catenin in body weight regulation
Professor David Grattan (Anatomy)
We have identified a novel brain response that occurs after eating a meal. The aim is to determine the role of this response in the normal regulation of food intake, and to determine whether abnormalities in this response might contribute to the development of obesity.
Other Otago Named Investigator: Dr Alexander Tups
Generating pulses with KNDy neurons
Professor Allan Herbison (Physiology)
The brain controls the levels of hormones circulating in the blood. The fertility hormones are secreted in a pulsatile manner that is essential for normal reproduction in humans. While it is known that it is the brain that generates pulsatile hormone secretion, how it does this has remained a complete mystery. This projects aims to build on a recent exciting discovery in the laboratory that has given us a clue as to the origin of fertility hormone pulsatility. Using genetically-manipulated mouse models and the very latest techniques in neuroscience we aim to elucidate and characterize the role of a small distinct group of brain cells we believe to be responsible for generating pulses of fertility hormones in the blood. Understanding how the brain controls fertility will lead to the development of new therapies for treating infertile couples in addition to new methods of contraception.
Other Otago Named Investigator: Dr Richard Piet
Timekeeping in the neural network controlling fertility
Dr Richard Piet (Physiology)
Fertility is controlled by a complex neuronal network in the brain that drives the activity of the gonadotropin releasing hormone (GnRH) neurons. This project aims to examine the mechanisms underlying the regulation of this neuronal network by the central biological clock in females. We will use state-of-the art experimental approaches in genetically-modified mouse models to dissect the specific brain circuits involved in keeping time within the GnRH neural network under both physiological and pathological conditions. We anticipate our studies will provide new information of the brain mechanisms involved in the control of reproductive function, and may open new avenues for therapeutic strategies for treating infertility in the clinic.
Other Otago Named Investigator: Dr Rebecca Campbell
CNE Public lecture - Valérie Simonneaux “Are humans a seasonal species?”
Monday 27 June at 5.30pm, Archway 2 Lecture Theatre, Union Street East, University of Otago, Dunedin
Valérie Simonneaux leads a research group dedicated to understanding the role of circadian and seasonal rhythms in regulating reproduction, and their various interactions. Prof. Simonneaux is a world expert in the molecular and cellular analysis of hypothalamic networks that control reproduction and metabolism and, in particular, has been responsible for delineating the pathways through which melatonin (the pineal gland hormone) acts on the brain to regulate fertility and body weight.
CNE Public Lecture Poster, Valérie Simonneaux (PDF 365 KB)
CNE Open Seminar Michael White "Cytokine signalling; the role of dynamics in the function of the NF=kB signalling system"
Wednesday 8 June 2016, at 5.30 pm in the Barnett Lecture
Professor Michael White of the University of Manchester, UK, Faculty of Life Sciences will be giving a CNE Open Seminar entitled "Cytokine signalling; the role of dynamics in the function of the NF-kB signalling system".
Mike White’s group has worked intensively on the dynamics and function of the NF-κB signalling system. In a landmark paper in Science in 2004, his group demonstrated that NF-κB oscillates between the cytoplasm and the nucleus of cells to regulate downstream gene expression. Subsequent high-profile papers examining multiple different cytokines have elaborated this principal of oscillations driving gene expression. Mike is a world expert at imaging signaling events within cells and directs the University of Manchester Systems Microscopy Centre that incorporates state-of-the-art equipment for multi-photon and confocal microscopy plus high throughput luminescence and fluorescence imaging.
The Otago School of Medical Science held a postgraduate symposium on 4th and 5th May at the Otago Museum. There were a number of prizes, with the winners of the two top prizes (Best Poster and Best Presentation) being invited to attend the University of Queensland Postgraduate Symposium in Brisbane later this year.
We are very pleased to announce that Mauro Batista da Silva (supervisor Rebecca Campbell) won the Best Presentation Prize. Congratulations Mauro.
Is Oxytocin the “love hormone”?
Oxytocin, often called the ‘love hormone’, can stimulate bonding behaviours in voles but is it really a ‘love hormone’ for humans? Dr Karl Iremonger and his team set out to see if giving oxytocin, in the form of a nasal spray, would make human subjects more lovey-dovey. As is often the case in science, the results were not as cut and dry as you might expect! Read more about Dr Iremongers oxytocin spray on the ODT website.
Nature Communications paper – Influence of AMH in the brain on PCOS
Centre for Neuroendocrinology researchers at the University of Otago are part of an international team of scientists who have discovered how anti-Müllerian hormone (AMH) may act in the brain to cause polycystic ovary syndrome (PCOS) symptoms.
Dr Rebecca Campbell was interviewed on Radio New Zealand about polycystic ovary syndrome (PCOS) and recent collaborative research investigating the role of anti-mullerian hormone action in the brain in this common endocrine disorder. http://www.radionz.co.nz/national/programmes/summerreport/audio/201785405/otago-uni-involved-in-cure-to-polycystic-ovary-syndrome
Science and Innovation Minister Steven Joyce visits CNE
Steven Joyce met with students and postdoctoral scientists from the Centre and attended the poster presentations of Papi Gustafson, Tessa Sanders, and Dr Aleisha Moore, the minister discussed aspects of the posters and asked where to next? Papi is completing writing her thesis and publications; Tessa has a post doctoral position at the National Institutes of Health, near Washington DC, US, studying cochlear development under Dr Matthew Kelley; Aleisha is joining the University of Mississippi Medical Centre in Jackson, Mississippi, US, to undertake a post-doctoral position with Prof. Mike Lehman.
How does maternal obesity affect the growing fetus?
Growing fetal brains are affected by their pregnant mother's obesity, and the effect can last for a lifetime, according to a new study by CNE neuroscientist Associate Professor Christine Jasoni. A Marsden grant has recently been awarded to Assoc. Prof. Jasoni to answer the question “does a leaky blood-brain barrier elevate the risk for obesity in the offspring of obese mothers?”
Brain “Connectomics” expert visits CNE
A world expert in the field of brain “connectomics” from Harvard University recently visited the Centre for Neuroendocrinology. Professor Jeff Lichtman was invited to Otago University as the 2015 Prestigious Eccles Speaker. The field of connectomics aims to study how brain cells are connected with one another. In order to study connections in the brain, Professor Lichtman has developed some sophisticated techniques to visualize brain cells and map them in precise detail. One of these techniques is called “Brainbow”. This involves targeting bright glowing molecules into brain cells such that different brain cells glow different colours of the rainbow. This allows the structure of brain cells to be seen and for their connections to be mapped. His laboratory has also been using powerful electron microscopes to see the smallest details of the brain. Powerful computing software is then used to “stitch” thousands of these images together to create a road map of brain connections. This research is shedding new light on how individual brain cells are connected with one another. In the future, these techniques will allow researchers to understand how brain connections are disrupted during neurodegenerative diseases and neurological disorders. Professor Lichtman’s visit was partially sponsored by CNE.
Professor Allan Herbison discusses the role of the brain and fertility on Radio New Zealand National
Having a baby has more to do with your brain that you might have thought. In this radio interview Professor Allan Herbison explains his research into the neuroendocrine control of fertility, and why one in every three cases of infertility can be put down to a failure of communication between the brain and the reproductive organs. Click here to hear more.
World-leading research by University of Otago scientists has shown which neurons flip a key ''fertility master switch'' in the brain.
Research published by Professor Allan Herbison, in the prestigious journal Proceedings of the National Academy of Sciences (PNAS), has provided solid evidence that neurons releasing kisspeptin drive the episodic hormone pulses needed for normal reproductive function. Dysfunction in this system could be related to many kinds of infertility. Read more about this work on the ODT website.
Otago researchers set to develop new diabetes treatment
A nutraceutical developed by University of Otago researchers that could help type II diabetes patients enjoy better regulation of their blood sugar levels has won the University’s 2015 Proof of Concept grant. The $50,000 grant, offered by the University's commercialisation arm, Otago Innovation, is aimed at transforming novel research at Otago into a marketable idea, product or service. Dr Alex Tups of the Centre for Neuroendocrinology, and Dr Phil Heyward (both of the Department of Physiology) are working on the nutraceutical, which involves a plant product. They are collaborating with Associate Professor Nigel Perry of Plant and Food Research and Pat Silcock, the Manager of Food Science’s Product Development Research Centre, who each bring essential expertise to the project.
Karl Iremonger was one of five University academics to be recognised in this year’s awards.
The Early Career Awards in Research recognise the University’s most promising early career researchers. Each recipient receives $5,000 to support their research and scholarship development. They also become members of the University’s O’Zone Group of early-to-mid-career researchers which promotes interdisciplinary thinking and collaborations within the University and beyond.
Dr Rebecca Campbell looks at brainwaves to find cause of syndrome affecting one in 10 women in New Zealand.
Polycystic ovarian syndrome (PCOS) affects nearly one in ten New Zealand women. The syndrome is linked to infertility and a number of health complications. New research by a team of scientists, led by Dr Rebecca Campbell, points to hormonal signals sent from the brain as the underlying cause of this all too prevalent illness. Read more about Dr Campbell’s work on this topic on the NZ Herald website.
Obesity and diabetes symptoms in mice improved by reversing brain inflammation
Using an antioxidant to reverse inflammation in the brain caused by a high-fat diet greatly improves symptoms related to obesity and type II diabetes, a new University of Otago-led study suggests.
The research, which appears in the leading international journal Diabetes, was led by Dr Alex Tups of the University’s Centre for Neuroendocrinology and Department of Physiology.
Dr Tups and an international team investigated whether directly stopping inflammatory processes in the brain’s hypothalamus could help lower blood sugar levels and reduce insulin resistance. In their research the team blocked a particular inflammatory signalling pathway (IKKβ/NF-κB) in the brains of obese mice. The researchers studied both mice that were obese due to a deficiency in the satiety hormone leptin and others due to a high-fat diet. The scientists administered butein to the mice to block the signalling pathway, which is involved in the body’s inflammatory immune responses. Butein is a flavonoid derived from plants traditionally used in Chinese herbal medicine.
Dr Tups says the team found that administering butein either directly into the brain or orally greatly improved glucose tolerance and brain insulin signalling in both types of obese mice. “We also showed that this profound effect was dose-dependent with better glucose tolerance achieved through higher doses of butein,” Dr Tups says.
The improved glucose tolerance of high-fat diet mice treated with the antioxidant was such that no difference was noticeable between them and low fat-diet mice that had not received butein. To confirm that activation of the IKKβ/NF-κB pathway plays a central role in metabolic obesity symptoms, the researchers also used a gene therapy technique to inhibit it in neurons in the hypothalamus. This gene therapy resulted in high-fat diet mice having a reduced body weight, building up less fat, expending more energy, and showing evidence of improved leptin-signalling.
Dr Tups says the study adds to growing body of evidence that a diet high in saturated fats activates a cascade of inflammatory processes in the brain which impair leptin and insulin signalling, leading to obesity and type II diabetes. “Our findings strongly support this idea and we also show that reversing this inflammation promotes a return towards normal metabolic functioning,” he says. The research suggests that butein and other natural compounds that block inflammation in the brain should be vigorously investigated as novel anti-diabetic treatments.
PhD students publish in prestigious journal
Two PhD students from the Centre of Neuroendocrinology have published papers in the prestigious journal, Proceedings of the National Academy of Sciences (PNAS).
Pauline Campos (supervisors Profs Allan Herbison & Brian Hyland) and Aleisha Moore (supervisors Dr Rebecca Campbell & Prof Allan Herbison) are both students in the CNE, and submitted their PhD theses in February of this year.
Pauline's research has focused on a small population of gonadotropin-releasing hormone (GnRH) neurons. The reproductive system is critically dependent upon pulsatile hormone release patterned and driven by these GnRH neurons. To date, the scattered distribution of the GnRH cell bodies remain the main limitation to investigating the cellular events that lead to pulsatile secretion of luteinizing hormone (LH). Using cutting edge technologies, the Herbison lab have generated a mouse model in which the GnRH neurons that control gonadotropin secretion can be selectively activated in living animals. They have been able to define how GnRH neurons generate a pulse of LH and this finding provides critical information for understanding and manipulating reproductive biology in mammals.
Aleisha's research focused on Polycystic ovarian syndrome (PCOS), which is the most common cause of infertility among women of reproductive age worldwide. Polycystic ovarian syndrome (PCOS) is the most common cause of infertility among women of reproductive age worldwide. Although PCOS is typically thought of as a disease of the ovaries, there is evidence that changes occur within neuronal circuits of the brain that control fertility. Using a mouse model of PCOS, the Campbell laboratory has identified abnormalities within a novel neuronal circuit that may underlie the development of PCOS symptoms. This work may lead to the production of novel therapeutic targets for the treatment of PCOS in women.
Pauline is now a research staff member in the Herbison lab, while Aleisha is doing a University of Otago Publishing Bursary with the aim to submitting a further paper.
Moore AM, Prescott M, Marshall CJ, Yip SH, Campbell RE. Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome. PNAS 2015 doi: 10.1073/pnas.1415038112. View abstract
Campos P and Herbison A.E. Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18387-92. doi: 10.1073/pnas.1415226112. Epub 2014 Dec 8. View abstract
Salt study makes breakthrough
New research, conducted by Professor Colin Brown and international colleagues, has pinpointed the mechanism salt uses to increase blood pressure. The article, published in the prestigious journal Neuron, describes how excessive salt interferes with hormonal safety measures which are meant to prevent high blood pressure. Read more about Professor Brown’s discovery on the ODT website.
Congratulations to Karl Iremonger - winner of the 2014 Prime Minister’s MacDiarmid Emerging Scientist Prize
Dr Karl Iremonger has won the 2014 Prime Minister’s MacDiarmid Emerging Scientist Prize in recognition of his discovery of a new brain cell structure and communication system.
- Read the Univesity of Otago' s press release
- 2014 Prime Minister’s MacDiarmid Emerging Scientist Prize
- Listen to Karl talking about his research on Radio New Zealand
Three CNE PIs awarded nearly $2 million in latest round of Marsden grants
Dr Rebecca Campbell (Associate Investigator (AI): Prof Allan Herbison) - awarded $820K over 3 years for her project "Functional dissection of a novel GABAergic pathway in the brain circuitry controlling fertility"
Dr Karl Iremonger (AI: Dr Valery Grinevich) awarded a Fast-Start grant of $300K over 3 years for his project "Oxytocin: a safety brake preventing excessive activation of the stress axis"
Associate Prof. Stephen Bunn (AI: Prof. Dave Grattan; Prof Brian Hyland) awarded $773K for his project "Memory impairments after stroke, a stressful condition"
From left: Rebecca Campbell, Karl Iremonger, Stephen Bunn.
Dr. Karl Iremonger awarded prestigious HRC Sir Charles Hercus Health Fellowship
Congratulations to Dr Karl Iremonger from the Department of Physiology who is the recipient of one of two Health Research Council (HRC) Sir Charles Hercus Fellowships. The Fellowships are extremely prestigious and he will use the four-year fellowship, valued at $489,062, to examine effects of chronic stress on the brain.
Prof Dave Grattan awarded $5 million HRC programme grant
Healthy Pregnancy, Healthy Babies
Professor Dave Grattan, Dr Christine Jasoni, and A/P Colin Brown (Physiology)
The most important time determining life-long health status of an individual is that spent developing in utero during pregnancy. To provide the optimal environment for development of her baby, the mother's body undergoes numerous changes. Apart from obvious adaptations in the uterus and breast, there are other equally-important changes, particularly in the brain; appetite increases, hormone secretion is altered, and moods and behaviour change. These adaptations are driven by pregnancy hormones, and in particular, prolactin and placental lactogen (PL). If these changes do not occur properly, complications may occur, including gestational diabetes, preterm labour, and postpartum depression. Such adverse events can also have serious consequences on the baby, changing brain development and increasing life-long risk of many diseases, including obesity and mental illness. This programme will evaluate how prolactin/PL helps the maternal brain adapt to pregnancy, and the consequences for the mother and baby when adaptive responses are compromised.