CNE News

April 2017

Summer student wins Dean’s prize

Julia Gouws (Supervisor Karl Iremonger) has been awarded the BMS Dean’s Prize for the best Summer Scholarship Report for 2016/17.  There were almost 50 reports to consider so this is a significant achievement, congratulations Julia.

 

The title of Julia’s summer research project was “Determining how chronically elevated levels of stress hormones affects neuronal excitability in female and male mice.”. The 10-week project involved using the genetically encoded calcium indicator GCaMP6f in order to determine how a model of chronic stress in mice affected CRH neuronal activity and whether there were sex differences in this activity. 

Julia is now undertaking a one-year Masters in the Centre for Neuroendocrinology, Physiology Department.

 

February 2017

South Island Cycle Challenge taken up by CNE

CNE members took up the challenge from the Physiology Department of Otago University to “Test your team's heart and 'cycle' around
the South Island of New Zealand”
…and when they say ‘cycle’ they’re talking just 10 minutes on an exercise bike – easy!

The challenge was to simply register a team of up to 4 people, who can cycle a total of 10 minutes – that’s only 2.5 minutes each if you want to share the load! The distance each team travels in 10 minutes will be plotted on our map of the South Island. With the help of all the Dunedin businesses we’re hoping to cycle as far as possible around the South Island. For each milestone reached along the way the Department of Physiology will also donate to the appeal.
cycle challenge team

There was a great turnout, and much fun had by all. Along with the Cycle Challenge and donations on the support page (link below if you wish to donate) almost $2,500 has been raised so far.

online at https://give.everydayhero.com/nz/south-island-cycle-challenge-2017

February 2017

New publication is editor's choice

Congratulations to Dr Xander Seymour on the publication of his paper  ‘Development of an excitatory kisspeptin projection to the oxytocin system in late pregnancy’ - this is an editor’s choice in J Physiol and is accompanied by a positive commentary from Bill Armstrong, one of the biggest names in oxytocin/vasopressin research.

Dr Xander Syemour

Seymour AJ, Scott V., Augustine RA, Bouwer GT, Campbell RE & Brown CH (2017). Development of an excitatory kisspeptin projection to the oxytocin system in late pregnancy. J. Physiol. Feb 1;595(3):825-838. View abstract

December 2016

PhD candidate produces exceptional thesis

Congratulations to Papi Gustafson who has had her doctoral thesis placed on the Health Sciences Divisional List of Exceptional Theses. The list comprises only those doctoral candidates whose research is assessed by examiners as being of an exceptional standard in every respect – research content, originality, quality of expression and accuracy of presentation – and amongst the top 10% of theses examined.
Papi successfully defended her thesis at a recent oral examination. The Convenors of Examiners both commented on the level of knowledge displayed by Papi, and her ability to defend and critique her own work.
Papi’s thesis, The role of prolactin in suppressing the maternal stress axis, looks at how the anterior pituitary hormone prolactin acts within the maternal brain to suppress stress-regulatory neurons and thus limit activation of the maternal stress response. The examiners were impressed with the high standard of Papi’s thesis and her level of dialogue throughout the oral exam. One examiner made a comment that “the thesis presents a major piece of original research which represents a significant and valuable contribution to knowledge in the field”. The Convenor of Examiners was also impressed, and noted that Papi demonstrated a depth of understanding of the topic rarely found in a PhD student.
Papi received the New Zealand Society of Endocrinology MediRay student speaker prize at the Queenstown Research Week conference held in 2015. Her research was supervised by Associate Professor Stephen Bunn and Professor Dave Grattan.

 

Papi Gustafson

Visit the Division of Health Sciences list of exceptional theses

 

 

November 2016

Major Marsden funding success for CNE researchers

Marsden success

The latest Royal Society of NZ Marsden Fund round has awarded 3-year project grants to four CNE researchers

Congratulations to Professor Allan Herbison, Professor David Grattan, Dr Alex Tups, and Professor Colin Brown who were awarded grants.

A brief outline of the projects are below:

Professor Colin Brown (Physiology)

Drinking for two: Central resetting of water balance in pregnancy and lactation ($825,000)

Pregnant women retain water during pregnancy to ensure an adequate blood supply for the developing baby and to prepare for milk production during lactation. Water is retained by increasing the secretion of vasopressin, a hormone that promotes water reabsorption in the kidneys. Normally, dilution of body salts by water retention decreases vasopressin secretion, but this doesn’t happen in pregnancy or lactation. While it has been known since the 1980s that altered vasopressin secretion resets water balance during pregnancy, the mechanisms that cause this resetting are still unknown. Our new data show that vasopressin-secreting cells are more sensitive to salt during lactation and so this might be the mechanism that resets water balance during pregnancy. Therefore, we will determine how vasopressin cells increase their responsiveness to salt in pregnancy to prepare women for successful pregnancy and lactation.

Professor David Grattan (Anatomy)

Growth factors mediating prolactin-induced neurogenesis in the adult brain ($810,000)

The aim of this project is to investigate the mechanisms by which the anterior pituitary hormone prolactin stimulates neurogenesis in the adult brain. The neural stem-cells do not express the prolactin receptor, but high expression is found in the choroid plexus, a structure that is considered part of the neurogenic niche. Using RNASeq to identify prolactin-responsive transcripts in the choroid plexus, we have discovered that prolactin induces expression of several growth factors. Here, we propose to investigate the hypothesis that these prolactin-sensitive growth factors secreted from the choroid plexus mediate the actions of prolactin to stimulate neurogenesis in subventricular zone of the maternal brain during pregnancy. We will measure expression of specific growth factors in the choroid plexus during pregnancy, and then determine whether expression of these growth factors changes in mice specifically lacking prolactin receptors in the choroid plexus. We will then investigate whether conditional deletion of specific growth factors in the choroid plexus abolishes the prolactin-induced increase in neurogenesis that normally occurs during pregnancy. The study will enhance our understanding of factors regulating the neurogenic niche in the adult brain, an area of intense interest in neuroscience because of its potential roles in neural plasticity and repair.

Professor Allan Herbison (Physiology):

In vivo gene editing with CRISPR to define estrogen feedback in the brain ($825,000)

Circulating levels of the ovarian hormone estrogen act on the brain to control fertility. A group of brain cells called the gonadotropin-releasing hormone (GnRH) neurons are responsible for controlling fertility in all mammals including humans. At present, the cellular pathway through which estrogen modulates the activity of GnRH neurons in unknown. This project intends to determine precisely which brain cells are responsible for detecting estrogen levels in the blood and transmitting this information to the GnRH neurons. We will use a novel application of CRISPR-Cas9 gene editing to delete estrogen receptors from GABA, glutamate or kisspeptin neurons located in two specific brain regions of the mouse. This research will develop world-leading in vivo gene editing technology for neuroscience within New Zealand and elucidate the mechanism of "estrogen feedback" to the GnRH neurons. This information will underpin the development of new strategies for helping infertile couples as well as the development of safer contraceptive agents.

Dr Alexander Tups (Physiology):

Hypothalamic Inflammation: Cause of leptin resistance and obesity? ($795,000)

Leptin, made by fat cells, is a hormone that usually tells the brain to stop eating. When people accumulate fat, leptin in the blood reaches very high unhealthy levels which make the brain unresponsive to the hormone. The loss of leptin action leads to the development of obesity and associated diseases such as type 2 diabetes. Saturated fats from a Western style diet lead to inflammation of the brain. This grant will explore whether this so called brain inflammation caused by dietary saturated fats is the cause of the loss of leptin responses and thereby the trigger for the development of obesity and type 2 diabetes.

For a full list of the grants awarded, see http://www.otago.ac.nz/news/news/otago625584.html

(Text from the University of Otago website)

Click here to read the ODT interview with the CNE recipients of this funding round.

HRC cupcakes

October 2016

Professor Colin Brown Inaugural Professorial Lecture

Professor Brown gave an engaging and entertaining talk spanning his career investigating oxytocin neurons

August 2016

PhD student awarded prize

Mauro Silva a PhD student in Rebecca Campbell’s Lab was awarded the New Zealand Society for Endocrinology Best Student Presentation Prize at The Medical Sciences Congress Meeting.  The meeting is part of Queenstown Research Week, this year being held in Nelson. A very successful year for Mauro.

 

June 2016

CNE PhD prize winner 2016 Mauro Silva

PhD prize winner

Congratulations to Mauro Silva (supervisor Dr Rebecca Campbell) who was awarded the CNE PhD Prize on 28th June.
The CNE PhD prize is open to all CNE 2nd year PhD students. The top three 2nd Year PhD students selected by the CNE Principal Investigators gave an oral presentation with an additional 10 minutes for questions. One of the judges was the CNE Lecturer for 2016 - Prof. Valerie Simonneaux of the Institut des Neurosciences Cellulaires et Intégratives, University of Strasbourg.

Mauro’s research is focused on trying to unveil neuronal and endocrine mechanisms underlying the pathophysiology of Polycystic Ovary Syndrome (PCOS), which is the main cause of female infertility throughout the world. To date, Mauro has discovered in an animal model of the syndrome that, even before the onset of puberty, the brain presents circuitry abnormalities and these are correlated with a disruption in female fertility in adulthood. Although this scenario looks negative, Mauro has also found that those altered brain circuits can be reversed by blocking the high androgen levels in the syndrome and, ultimately, restore fertility.

 

June 2016

Research Milestone for Professor

Allan_Herbison

With his most recent publication (1 June 2016) Prof. Allan Herbison, Department of Physiology, has reached the very significant landmark of 200 peer-reviewed journal article publications.

This achievement is outstanding - not only in quantity, but in quality and impact. Professor Herbison has over 13,000 citations and an H index of 64.

The three most highly-cited publications from work undertaken in Physiology have been those working with Seong-Kyu Han (1), Rebecca Campbell and Rob Porteous (2), and Jenny Clarkson (3).

1. Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK, Clifton DK, Steiner RA, Herbison AE. (2005) Activation of gonadotropin-releasing hormone (GnRH) neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 25, 11349-11356. [662 citations]

2. Wintermantel T*, Campbell RE*, Porteous R, Bock D, Gröne HJ, Todman MG, Korach KS, Greiner E, Perez CA, Schütz G, Herbison AE. (2006) Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons and fertility. Neuron 52, 271-280. [355 citations]

3. Clarkson J, Herbison AE. (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology, 147, 5817-5825. [510 citations]

June 2016

CNE investigators awarded 4 HRC project grants in 2015/16 round

 

HRC Granrt Recipients

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)

$1,189,211
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)
$1,195,100

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)
$1,121,058

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)
$1,074,371

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

 

June 2016

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

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 Professor 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

8 June 2016

8 June 2016: CNE Open Seminar Prof. 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.

 

May 2016

Student success

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.

 

February 2016

Is Oxytocin the “love hormone”?

Described as the "love hormone'', oxytocin might increase empathy, but it'd pay not to spray it up your nose, writes brain-cell expert Karl Iremonger.

You may have heard oxytocin referred to as the "love hormone''.

But before you go out this Valentine's Day to procure large quantities of the neuropeptide to sprinkle about, take a moment to find out about the science behind this little hormone.

Oxytocin is a signalling molecule produced by brain cells. It is very similar in chemical structure to another signalling molecule produced in the brain, vasopressin.

As well as being released into the brain, oxytocin and vasopressin are also released into the bloodstream and travel all around the body. The stimuli that trigger the release of these molecules includes sexual stimulation, childbirth, breast-feeding, stress, and dehydration.

Thankfully, release of these molecules does not require these stimuli to all happen at once.

Once released into the body, vasopressin acts on the kidneys to help prevent dehydration, whereas oxytocin acts on the uterus to facilitate childbirth as well as on the mammary glands to induce milk release for breast-feeding.

These hormones are found in many species, including humans and rodents, but similar molecules are even found in worms and pond snails.

Recent research is unravelling the role oxytocin and vasopressin play in regulating brain function, with evidence that these hormones play an important role in regulating social behaviour, partner preference, parental bonding, stress and anxiety.

Remarkably, research on a rodent called the prairie vole has provided some of the most interesting results.

These animals are found on the plains of North America where they enjoy digging holes. Once they find a mate, they partner with that mate for life.

This behaviour critically depends on the release of oxytocin and vasopressin within the brain.

Artificially elevating oxytocin or vasopressin levels in these voles can artificially induce this bonding behaviour.

The fact that oxytocin can regulate social behaviour in rodents has led scientists to test whether this molecule can regulate social behaviour in humans.

Unfortunately, the oxytocin and vasopressin molecules are large in size and have difficulty diffusing into the brain.

One novel (yet controversial) method of delivering oxytocin into the brain of humans is to puff it up the nose with a nasal spray.

Studies using oxytocin nasal spray have concluded that oxytocin delivered via this route can induce small changes in the activity of areas of the brain known to be important in processing social cues and regulating fear responses.

Other studies have reported it may increase trust and empathy and reduce anxiety.

It is important to note, however, that these effects on behaviour are highly variable and depend both on the individual and the social situation.

One proposed explanation for this is that some people respond differently to oxytocin due to slight differences in their DNA.

This idea has led researchers to investigate whether the DNA code for the oxytocin receptor is different in people with certain neurological conditions that are associated with social deficits, for example, autism spectrum disorder.

So before you go out and spend your next pay on a supersized box of oxytocin nasal spray, it is important to know that the effects of these molecules are complex and not completely understood.

Unfortunately, a brief puff of these molecules is unlikely to make someone fall in love with you in an instant. That is, unless you are a prairie vole.

• Dr Karl Iremonger is a researcher and lecturer at the University of Otago department of physiology and carries out his research in the Centre for Neuroendocrinology. He was awarded the 2014 Prime Minister's MacDiarmid Emerging Scientist Prize after discovering a new brain cell structure and communication system, setting the stage for more targeted therapies for neurological diseases.

reprinted from the Otago Daily Times

January 2016

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.
http://www.otago.ac.nz/news/news/otago440203.html

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

December 2015

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.

 

 

November 2015

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?”

November 2015

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.

October 2015

Professor Allan Herbison discusses the role of the brain and fertility on Radio New Zealand National

Having a child can be a real challenge!
It's estimated that a quarter of couples trying to conceive in NZ struggle to do so. Traditional thinking has placed an emphasis on things going wrong 'below the belt', with either the eggs or the sperm. But could it also be in the mind? …

Link to Radio NewZealand "This Way Up" broadcast

October 2015

World-leading research by University of Otago scientists has shown which neurons flip a key ''fertility master switch'' in the brain.

World-leading research by University of Otago scientists has shown which neurons flip a key ''fertility master switch'' in the brain.
And this research, led by Prof Allan Herbison, at the Otago University Centre for Neuroendocrinology, could help pave the way for further advances in infertility treatment. The Otago-led researchers have just published the first direct evidence that it was kisspeptin neurons working in concert that generate the small, episodic hormone pulses that are crucial to normal reproductive functioning in humans and other mammals.
The findings were published this week in the prestigious journal Proceedings of the National Academy of Sciences (PNAS).

Further reading in ODT article

September 2015

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.

Further reading on University of Otago website

August 2015

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.

 

August 2015

Dr Rebecca Campbell looks at brainwaves to find cause of syndrome affecting one in 10 women in New Zealand.

Polycystic ovarian syndrome, or PCOS as it's more commonly known,  is linked to infertility and multiple chronic health problems such as diabetes, higher blood pressure, cancer of the womb and abnormal cholesterol.A recent study by Dr Rebecca Campbell and her team at the Centre for Neuroedocrinology, Otago University revealed a completely unexpected brain pathway within the GnRH neuronal network that might underpin the neuroendocrine abnormalities of PCOS.

Further reading in the NZ Herald article here

 

January 2015

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.

January 2015

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

 

January 2015

Salt study makes breakthrough

 

We have been told for years to limit our salt intake for the sake of our health.

Now, new research carried out on rats, partly conducted at the University of Otago, has discovered how salt affects a part of the brain that controls blood pressure.

Researchers said in a press release more research was needed on whether the same thing happened in humans, and how it might be reversed. The link between salt and hypertension is well known, but the research demonstrated a brain mechanism by which salt affects blood pressure by altering neurons that release the hormone vasopressin. Excessive salt interfered with the natural safety mechanism that prevented high blood pressure, when ingested over a long period.

Published in the journal Neuron, the research was led by McGill University, in Montreal, and involved researchers in four countries, showing the value of international research, Otago neuroendocrinologist and salt study researcher Associate Prof Colin Brown said. ''This was a truly international collaboration.'' Otago's contribution was testing the electrical activity of single brain cells in anaesthetised rats at the same time as recording their blood pressure. Only a handful of laboratories in the world were able to conduct that experiment, Prof Brown said.

Prof Brown said the research reinforced existing messages about salt intake, but did not change its safety profile. ''It doesn't change that fundamental message. But it does give us an explanation of why.'' Prof Brown said the research could possibly be used to develop drugs for certain kinds of hypertension, but warned it did not mean the development of a ''wonder drug''. Hypertension was like cancer, in the sense that it had many types, he said.

Link to article originally in Otago Daily Times, 27 January 2015

December 2014

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

Watch a short clip of Karl talking about his research

November 2014

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"

November 2014

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.

June 2014

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.

Centre for Neuroendocrinology Centre for Neuroendocrinology University of Otago