Medicine and Health Sciences Commons^™

Neurotrophin Signaling And Alzheimer's Disease Neurodegeneration - Focus On Bdnf/Trkb Signaling, Jenny Wong

Illawarra Health and Medical Research Institute

Neurotrophins are small proteins vital for neuronal growth, differentiation, survival, and plasticity. Members of the mammalian neurotrophin family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin- 4/5 (NT-4/5). Their neurotrophic effects are mediated by the tropomyosin receptor kinase (Trk) receptors, membrane-bound receptor tyrosine kinases (NGF for TrkA, BDNF and NT4/5 for TrkB, and NT-3 for TrkC) which activate various cell signaling pathways linked to growth, differentiation, and survival. The importance of neurotrophin signaling in brain development is highlighted by findings showing that knockout mice for any one of the neurotrophins or their receptors are fatal …

Structural And Functional Aspects Of Hetero-Oligomers Formed By The Small Heat Shock Proteins Αb-Crystallin And Hsp27, J Andrew Aquilina, Sudichhya Shrestha, Amie M. Morris, Heath Ecroyd

Illawarra Health and Medical Research Institute

Small heat shock proteins (sHSPs) exist as large polydisperse species in which there is constant dynamic subunit exchange between oligomeric and dissociated forms. Their primary role in vivo is to bind destabilized proteins and prevent their misfolding and aggregation. αB-Crystallin (αB) and HSP27 are the two most widely distributed and most studied sHSPs in the human body. They are coexpressed in different tissues, where they are known to associate with each other to form hetero-oligomeric complexes. In this study, we aimed to determine how these two sHSPs interact to form hetero-oligomers in vitro and whether, by doing so, there is …

Dha Prevents Altered 5-Ht1a, 5-Ht2a, Cb1 And Gabaa Receptor Binding Densities In The Brain Of Male Rats Fed A High-Saturated-Fat Diet, Yinghua Yu, Yizhen Wu, Craig Patch, Zhixiang Wu, Alexander Szabo, Duo Li, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Low levels of docosahexaenoic acid (DHA) have been linked to a number of mental illnesses such as memory loss, depression and schizophrenia. While supplementation of DHA is beneficial in improving memory and cognition, the influence of dietary fats on the neurotransmitters and receptors involved in cognitive function is still not known. The aim of this study was to investigate serotonin receptor (5-HT_1A and 5-HT_2A), cannabinoid receptor (CB1) and gamma-aminobutyric acid type A (GABA_A) receptor binding densities in the brain of male rats fed a high-saturated-fat (HF) diet, as well as the effect of DHA supplementation …

Preventing Help-Negation For Suicidal Ideation: Implications For Thwarted Belongingness, Social Network Size And Frequency Of Social Interaction, Alexander Svenson, Coralie J. Wilson, Peter Caputi

Illawarra Health and Medical Research Institute

Poster presented at the National Suicide Prevention Conference, Melbourne Australia, July 2013

Help-negation is seen when the severity of an individual's suicidal ideation increases and they become less likely to seek help as a result of their condition. Research has implicated distorted affect regulation and perceptual processes related to social support in the development of help-negation among suicidal individuals (Wilson et al., 2013). Future research needs to focus on psycho-social factors that can be linked to neurological processes that differentiate suicidal individuals from controls and are directly implicated in the help-negation processes associated with suicidal ideation. As suicidal individuals have …

Reciprocity As Deliberative Capacity: Lessons From A Citizens Deliberation On Carbon Pricing Mechanisms In Australia, Alex Y. Lo, Kim S. Alexander, Wendy Proctor, Anthony Ryan

Illawarra Health and Medical Research Institute

Australia has seen a deep division in opinion in search of a carbon pricing mechanism. While concepts of carbon taxation and emission trading have comparable public support, climate scepticism is influencing the debates in political and public spheres in downplaying the need for carbon pricing. Public deliberation is a possible engagement option to address the conflict inherent in climate policy preferences. This research explores the way that a deliberative forum involving twenty-four Australians promoted effective communication between participants through which conflict between policy preferences became more tangible. While the forum did not eliminate disagreement in preferences in the choice of …

Pregnancies Following The Use Of Balloon Tamponade Technology In The Previous Pregnancy, C Georgiou

Illawarra Health and Medical Research Institute

Abstract of an E-posters that presented at the RCOG World Congress 2013, 24-26 June 2013, Liverpool, United Kingdom.

Effects Of Antipsychotic Medications On Appetite, Weight, And Insulin Resistance, Chao Deng

Illawarra Health and Medical Research Institute

Although clozapine, olanzapine, and other atypical antipsychotic drugs (APDs) have fewer extrapyramidal side effects, they have serious metabolic side effects such as substantial weight gain, intra-abdominal obesity, and type 2 diabetes mellitus. Given that most patients with mental disorders face chronic, even life-long, treatment with APDs, the risks of weight gain/obesity and other metabolic symptoms are major considerations for APD maintenance treatment. This review focuses on the effects of APDs on weight gain, appetite, insulin resistance, and glucose dysregulation, and the relevant underlying mechanisms that may be help to prevent and treat metabolic side effects caused by APD therapy.

Laparoscopic Management Of An Adnexal Mass During The Second Trimester Of Pregnancy, C Georgiou

Illawarra Health and Medical Research Institute

Abstract of paper presented at AGES XXIII Annual Scientific Meeting, Brisbane, 2013.

Benefits, Issues, And Recommendations For Personalized Medicine In Oncology In Canada, C Butts, S Kamel-Reid, G Batist, S Chia, C Blanke, M Moore, M B. Sawyer, C Desjardins, A Dubois, J Pun, K Bonter, F D. Ashbury

Illawarra Health and Medical Research Institute

The burden of cancer for Canadian citizens and society is large. New technologies have the potential to increase the use of genetic information in clinical decision-making, furthering prevention, surveillance, and safer, more effective drug therapies for cancer patients. Personalized medicine can have different meanings to different people. The context for personalized medicine in the present paper is genetic testing, which offers the promise of refining treatment decisions for those diagnosed with chronic and life-threatening illnesses. Personalized medicine and genetic characterization of tumours can also give direction to the development of novel drugs. Genetic testing will increasingly become an essential part …

The Key Regulatory Roles Of The Pi3k/Akt Signaling Pathway In The Functionalities Of Mesenchymal Stem Cells And Applications In Tissue Regeneration, Jiezhong Chen, Ross Crawford, Chen Chen, Yin Xiao

Illawarra Health and Medical Research Institute

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity …

Author Reply, John Carmody, Victoria Traynor, Don C. Iverson, Elena M. Marchetti

Illawarra Health and Medical Research Institute

We thank Regal[1] for his interest and his kind comments regarding our paper.[2] Our principal aim was to highlight several key ethical issues faced by Australian physicians (e.g. reporting obligations, negative consequences of driving cessation). Regal raises a challenging, yet unresolved, dilemma: which test best determines safe driving capacity? Although an in-depth appraisal of existing tests was beyond the scope of our paper, we did refer to two seminal reviews. The Australian and New Zealand Society of Geriatric Medicine (ANZSGM)[3] and the American Academy of Neurology (AAN)[4] have comprehensively reviewed the existing literature regarding assessment of fitness to drive of …

Novel Implications Of Lingo-1 And Its Signalling Partners In The Dorsolateral Prefrontal Cortex In Schizophrenia, Jessica L. Andrews, Kelly A. Newell, Xu-Feng Huang, Francesca Fernandez-Enright

Illawarra Health and Medical Research Institute

No abstract provided.

Analysis Of The Psychological Impact Of A Vascular Risk Factor Intervention: Results From A Cluster Randomized Controlled Trial In Australian General Practice, Suzanne Helen Mckenzie, Upali W. Jayasinghe, Mahnaz Fanaian, Megan Passey, Mark Fort Harris

Illawarra Health and Medical Research Institute

Background Screening for vascular disease, risk assessment and management are encouraged in general practice however there is limited evidence about the emotional impact on patients. The Health Improvement and Prevention Study evaluated the impact of a general practice-based vascular risk factor intervention on behavioural and physiological risk factors in 30 Australian practices. The primary aim of this analysis is to investigate the psychological impact of participating in the intervention arm of the trial. The secondary aim is to identify the mediating effects of changes in behavioural risk factors or BMI. Methods This study is an analysis of a secondary outcome …

Sleep-Wake Behaviour And The Eeg In Altered States Of Consciousness, Sarah P. Loughran, Sabine Regel, Lilith Buetler, Martin Wieser, Robert Riener, Peter Achermann

Illawarra Health and Medical Research Institute

Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australia.

Central Administration Of Palmitic Acid Increases Food Intake And Body Temperature In Male Sprague Dawley Rats, Chi H. L Dinh, Alexander M. Szabo, Hongqin Wang, Yinghua Yu, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Abstract of a poster presentation at the World Diabetes Congress 2013

Rapid Quantification Of Free Cholesterol In Tears Using Direct Insertion/Electron Ionization-Mass Spectrometry, Xiaojia Eric Wei, John Korth, Simon H. J Brown, Todd W. Mitchell, Roger J. W Truscott, Stephen J. Blanksby, Mark D. P Willcox, Zhenjun Zhao

Illawarra Health and Medical Research Institute

Purpose. To establish a simple and rapid analytical method, based on direct insertion/electron ionization–mass spectrometry (DI/EI-MS), for measuring free cholesterol in tears from humans and rabbits.

Methods. A stable-isotope dilution protocol employing DI/EI-MS in selected ion monitoring mode was developed and validated. It was used to quantify the free cholesterol content in human and rabbit tear extracts. Tears were collected from adult humans (n = 15) and rabbits (n = 10) and lipids extracted.

Results. Screening, full-scan (m/z 40–600) DI/EI-MS analysis of crude tear extracts showed that diagnostic ions located in the mass range m/z 350 to 400 were those …

Burden And Support Needs Of Carers Of Persons With Borderline Personality Disorder: A Systematic Review, Rachel Bailey, Brin F. S Grenyer

Illawarra Health and Medical Research Institute

Background: A major feature of personality disorders is significant impairment in interpersonal functioning, which may create challenges in close relationships. This article aims to systematically review the experience of carers of persons with personality disorders. Method: The PRISMA systematic review method was followed, and empirical studies written in English, published between 1996 and 2011, and cited in major electronic databases were searched. Studies meeting the following selection criteria were included: (1) carers or families of persons with personality disorders; (2) intervention involving the carers or families; (3) burden or related construct used. Studies were required to meet either criteria 1 …

An Improved High-Throughput Lipid Extraction Method For The Analysis Of Human Brain Lipids, Sarah K. Abbott, Andrew M. Jenner, Todd W. Mitchell, Simon H. Brown, Glenda M. Halliday, Brett Garner

Illawarra Health and Medical Research Institute

We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass-glass homogenization) was compared to a high-throughput method combining methyl-tert-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass-glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, …

Novel Behavioural Characteristics Of The Appswe/Ps1Δe9 Transgenic Mouse Model Of Alzheimer's Disease, David Cheng, Warren Logge, Jac Kee Low, Brett Garner, Tim Karl

Illawarra Health and Medical Research Institute

In order to better understand animal models of Alzheimer's disease, novel phenotyping strategies have been established for transgenic mouse models. In line with this, the current study characterised male APPxPS1 transgenic mice on mixed C57BL/6JxC3H/HeJ background for the first time for social recognition memory, sensorimotor gating, and spatial memory using the cheeseboard test as an alternative to the Morris water maze. Furthermore, locomotion, anxiety, and fear conditioning were evaluated in transgenic and wild type-like animals. APPxPS1 males displayed task-dependent hyperlocomotion and anxiety behaviours and exhibited social recognition memory impairments compared to wild type-like littermates. Spatial learning and memory, fear conditioning, …

Analysis Of Subcellular [57co] Cobalamin Distribution In Sh-Sy5y Neurons And Brain Tissue, Hua Zhao, Kalani Ruberu, Hongyun Li, Brett Garner

Illawarra Health and Medical Research Institute

Cobalamin (Cbl) utilization as a cofactor for methionine synthase and methylmalonyl-CoA mutase is dependent on the transport of Cbl through lysosomes and its subsequent delivery to the cytosol and mitochondria. We speculated that neuropathological conditions that impair lysosomal function (e.g., age-related lipofuscinosis and specific neurodegenerative diseases) might impair lysosomal Cbl transport. To address this question, an appropriate method to quantify intracellular Cbl transport in neuronal cell types and brain tissue is required. Thus, we developed methods to measure [⁵⁷Co] Cbl levels in lysosomes, mitochondria and cytosol obtained from in vitro and in vivo sources. Human SH-SY5Y neurons or …

Ascertaining Invasive Breast Cancer Cases; The Validity Of Administrative And Self-Reported Data Sources In Australia, Anna Kemp, David B. Preen, Christobel Saunders, C D'Arcy J. Holman, Max Bulsara, Kris Rogers, Elizabeth E. Roughead

Illawarra Health and Medical Research Institute

Background: Statutory State-based cancer registries are considered the ‘gold standard’ for researchers identifying cancer cases in Australia, but research using self-report or administrative health datasets (e.g. hospital records) may not have linkage to a Cancer Registry and need to identify cases. This study investigated the validity of administrative and self-reported data compared with records in a State-wide Cancer Registry in identifying invasive breast cancer cases. Methods: Cases of invasive breast cancer recorded on the New South Wales (NSW) Cancer Registry between July 2004 and December 2008 (the study period) were identified for women in the 45 and Up Study. Registry …

Reduction Of Histamine H1 Receptor Binding Induced By High-Fat Diet Can Be Prevented By Dha And Dietary Fiber In Specific Brain Areas Of Male Rats, Zhixiang Wu, Yinghua Yu, Yizhen Wu, Craig S. Patch, Alexander Szabo, Xu-Feng Huang

Illawarra Health and Medical Research Institute

High-fat (HF) diet and obesity are risk factors for a number of mental health problems including depression, cognitive dysfunction, dementia, and neurodegenerative diseases. Histamine H1 receptors (H1Rs) are involved in many of these conditions. This study examined H1R receptor binding density in the brain of male rats fed a high-saturated fat (HF) diet, as well as the effect of docosahexaenoic acid (DHA), galacto-oligosaccharide (GOS) and resistant starch (RS) supplementation of HF diet. Alterations of H1R expression in the post-mortem rat brain were detected by [ 3H]-pyrilamine binding autoradiography. We found that HF diet significantly decreased H1R binding densities in the …

In Vivo Pharmacological Evaluations Of Novel Olanzapine Analogues In Rats: A Potential New Avenue For The Treatment Of Schizophrenia, Somayeh Jafari, Xu-Feng Huang, Jessica L. Andrews, Francesca Fernandez-Enright

Illawarra Health and Medical Research Institute

Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4′-methylpiperazin-1′-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4′-methyl-1′,4′-diazepan-1′-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally …

Neural Correlates Of Successful Encoding In Schizophrenia: An Event-Related Potential Study, Amity Green, Paul Fitzgerald, Patricia T. Michie, Pradeep Nathan, Rodney J. Croft

Illawarra Health and Medical Research Institute

Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australia.

Characterization Of Forebrain Neurons Derived From Late-Onset Huntington's Disease Human Embryonic Stem Cell Lines, Jonathan C. Niclis, Anita Pinar, John M. Haynes, Walaa Alsanie, Robert Jenny, Mirella Dottori, David S. Cram

Illawarra Health and Medical Research Institute

Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin (HTT) gene. Recently, induced pluripotent stem cell (iPSC) lines carrying atypical and aggressive (CAG60+) HD variants have been generated and exhibit disparate molecular pathologies. Here we investigate two human embryonic stem ce ll (hESC) lines carrying CAG₃₇ and CAG₅₁ typical late-onset repeat expansions in comparison to wildtype control lines during undifferentiated states and throughout forebrain neuronal differentiation. Pluripotent HD lines demonstrate growth, viability, pluripotent gene expression, mitochondrial activity and forebrain specification that is indistinguishable from control lines. Expression …

Rho/Rock Pathway Is Essential To The Expansion, Differentiation, And Morphological Rearrangements Of Human Neural Stem/Progenitor Cells Induced By Lysophosphatidic Acid, Frisca Frisca, Duncan E. Crombie, Mirella Dottori, Yona Goldshmit, Alice Pebay

Illawarra Health and Medical Research Institute

We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC). We extended these studies by analyzing LPA's effects on the expansion of neural stem/ progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed whether data obtained on the neural differentiation of hESCs were relevant to iPSCs. We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation. We demonstrated that LPA inhibited the expansion of NS/PCs of both origins, mainly by increased apoptosis in a Rho/Rho-associated kinase …

Lipid Anti-Lipid Antibody Responses Correlate With Disease Activity In Systemic Lupus Erythematosus, Vojislav Jovanovic, Nurhuda Abdul Aziz, Yan Ting Lim, Amanda Ng Ai Poh, Sherlynn Jin Hui Chan, Eliza Ho Xin Pei, Fei Chuin Lew, Guanghou Shui, Andrew M. Jenner, Li Bowen, Eoin F. Mckinney, Paul A. Lyons, Michael D. Kemeny, Kenneth G.C. Smith, Markus R. Wenk, Paul A. Macary

Illawarra Health and Medical Research Institute

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using …

Mouse Strain-Dependent Variation In Obesity And Glucose Homeostasis In Response To High-Fat Feeding, M K. Montgomery, N L. Hallahan, S H. Brown, M Liu, T W. Mitchell, G J. Cooney, N Turner

Illawarra Health and Medical Research Institute

Aims/hypothesis: Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated strain-dependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N). Methods: Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to …

Increased Apolipoprotein D Dimer Formation In Alzheimer's Disease Hippocampus Is Associated With Lipid Conjugated Diene Levels, Surabhi Bhatia, Andrew M. Jenner, Hongyun Li, Kalani Ruberu, Adena S. Spiro, Claire E. Shepherd, Jillian J. Kril, Nupur Kain, Anthony Don, Brett Garner

Illawarra Health and Medical Research Institute

Previous studies indicate that apolipoprotein D (apoD) may have a lipid antioxidant function in the brain. We have shown that apoD can reduce free radical-generating lipid hydroperoxides to inert lipid hydroxides in a reaction that involves conversion of surface exposed apoD methione-93 (Met93) residue to Met93-sulfoxide (Met93-SO). One consequence of this reaction is the formation of a stable dimerized form of apoD. As cerebral lipid peroxidation is associated with Alzheimer's disease (AD), in the present study we aimed to assess the possible presence of apoD dimers in postmortem hippocampal and cerebellar tissues derived from a cohort of pathologically defined cases …

Recent Advance In The Studies Of Beta-Glucans For Cancer Therapy, Jiezhong Chen

Illawarra Health and Medical Research Institute

Mushroom has been used for thousand years in China and other Asian countries for health improvement and treatment of disease. A few decades ago, its main component beta-gluean was identified. Beta-glueans are now known to have beneficial effects for the prevention and treatment of many diseases including eanccr, infectious disease, hyperlipidemia, diabetes, atherosclerosis and obesity. The effects are mediated by the different properties of beta-glucans such as immune stimulation and bile acid trapping.