Dr Doug Smith

Dr Doug Smith

Senior Lecturer

School of Biomedical Sciences and Pharmacy (Anatomy)

The age of reason

Dr Doug Smith is investigating the impacts of ageing on the nervous system, with the aim of identifying interventions that will extend healthspan.

Lifespan encapsulates the number of years you are alive, whereas healthspan refers to the number of years you maintain mental and physical health, without serious disease, during your lifespan.

Dr Doug Smith wants you to live better for longer. That doesn't necessarily mean living for longer, although that may be a benefit of good health. He isn't interested in finding the elixir of youth, just the key to maximum healthspan. 

"Some people want to live forever, I have no interest in extending lifespan, I want to extend healthspan, it's a very different thing," he explains.

With life expectancy increasing and family sizes decreasing, our national population is ageing fast, prompting urgency in research in this field.

"In about 20 years from now, there are going to be more people living in Australia who are over the age of 65 then under the age of 15," Doug asserts.

"If more people reach their latter years still in pretty good shape, physically and mentally, then presumably we can lessen the health care cost burden."

"And more importantly, those people will have a better quality of life."

NERVOUS SYSTEMS

With a background in neurobiology, Doug is focusing his study on the impacts of ageing on the nervous system.

The central nervous system (CNS) includes the brain and spinal cord, whilst the peripheral nervous system (PNS) comprises all the body's nerve pathways outside of the CNS. Both the CNS and PNS are affected by ageing.

For example, declining senses, slowing of messages controlling movements, a loss of clarity in cognitive processes and failing memory are all nervous system specific changes that have been attributed to ageing.   

Using an animal model to study the ageing brain, spinal cord and vestibular (balance) system, Doug and his collaborators hope to further understand these changes on a cellular and molecular level.

Together with his team, Doug uses modern genomics approaches, such as next generation sequencing, to obtain a global picture of age-related gene expression changes to inform their directions in the lab.

"There is much more that we don't know than we do know, so doing a discovery driven approach first, that can then can direct us, is very powerful," he says.

Doug and his team then use more traditional hypothesis driven approaches when looking to confirm or refute possible truths suggested by the broader genomics data.

MICRODISSECTION

Utilising laser-capture microdissection (LCMD) technology, the team are able to identify and extract specific cell types from the highly complex nervous system for study.

For example, LCMD extraction allows the team to investigate the effects of ageing on dopamine neurons, the degeneration of which causes Parkinson's disease. They also investigate the breakdown of the blood brain barrier, which is seen in vascular dementia.

Another study saw the team comparing levels of mitochondrial DNA mutation in young and old tissue. Mitochondria are the power generators of a cell and they have their own very small genome. Age-related mutations in this genome are thought to compromise the ability of mitochondria to generate energy for the myriad of cell activities needed for proper nervous system function.

"Based on our genomics findings we are now doing a lipidomics investigation," Doug explains. 

"The CNS is chock full of different types of lipids, and we know they change with ageing, so we are trying to understand those changes in greater detail."

"Once we align these various approaches, it will give us a really good indication of where to head in terms of our more focused or directed studies."

THE NEXT GENERATION SEQUENCERS

Doug credits PhD and undergrad students with undertaking the bulk of the laborious lab work.

"We are always looking for more students who are passionate about biology and who would like to work with us," Doug says and adds, laughing, "Bring your own money!"

A senior lecturer in the School of Biomedical Sciences and Pharmacy, Doug admits that although teaching drains research time and energy, it actually enhances his outcomes.

"I actually believe that teaching is good for your research because when you teach you have to stand back and take a bigger picture view of things," he says.

"And when you do that, sometimes it gives you a different perspective for your research."

Doug was a post-doctoral scientist when a fascination with the biological phenomenon of ageing drew him to this field of study.

"I have always been curious, I have always wanted to know how things work," he conveys.

"Age related degeneration just doesn't make much sense. A lot of energy and effort goes into creating a sexually mature organism. So, why not then just maintain it? I find it very interesting."

AGEING GRACEFULLY

Although studies across species and domains show that ageing has a major impact on both the animal and human body, some individuals seem somewhat resilient to the effects of ageing.

"Everybody has a grandma or elderly uncle that still seems to be running around like a sprightly 30 or 40 year old, both mentally and physically they are doing really well," Doug acknowledges.

"We are trying to determine what it is about these individuals that allows them to have such a good healthspan."

"A potentially disappointing outcome of our work would be that we find out what the cause or causes of ageing are, but we can't find an intervention."

"However, there are many examples of people ageing well, and if you look at what they do, they are all pretty active, not just physically but mentally as well."

FREEDOM OF CHOICE

Due to the mounting evidence, Doug suggests it is more realistic to earn a longer healthspan, than win one in the unexplained resilience to ageing jackpot.

He refers to several existing intervention studies that show vastly different outcomes for participants relative to different diets and levels of exercise.

But don't wait too long. Evidence emerging from Doug's lab suggests the ageing process begins much earlier than we would like to believe.

"Preliminary data is certainly indicating that if you are going to live well, you can't wait until you are 75 and then decide to make healthier choices."

In the end, the solution to retarding the ageing process may simply involve choices around modifying behaviour.

"Once we characterise some of the processes of normal ageing, we can then go and see if a high fat, high sugar, Omega 3, or resveratrol diet, and/or exercise, are going to change the ageing process at the molecular, cellular, organ and whole body levels," Doug explains.

"The next step would be to design interventions that can be applied to human populations. Humans won't like some of the dietary restrictions, or the exercise. The red wine they might go for," he smiles.

"People will always have free will. We are just trying to figure out ways that are acceptable to the majority to help them to age well and stay active for longer."

The age of reason

Dr Doug Smith is investigating the impacts of ageing on the nervous system, with the aim of identifying interventions that will extend healthspan.

Read more

Career Summary

Biography

The main aim of my lab's research is to better understand the effects of ageing on nervous system function. It is well known that the world's population is ageing and soon there will be more people over the age of 65 than there are children. If we are to improve the quality of life of the aged, then we must first understand how ageing affects the body's various physiological systems. As the nervous system has an important role in most functions, its preservation with ageing is paramount.

We are primarily using molecular approaches and focusing on ageing-related changes in the cell's two genomes - the nuclear and mitochondrial genomes. It is well-established that both genomes accumulate mutations with ageing, although it is not completely clear whether these mutations are more detrimental to cell function if they accumulate more so in one of the genomes as opposed to the other. It is also not known whether the mutation accumulations occur in a cell-specific manner. This is particularly important for the nervous system with its highly heterogeneous cell population. A number of nervous system functions appear more susceptible to the ageing process than others. For example, the special senses of hearing, vision and balance are particularly prone, although it remains to be determined whether the peripheral components of these systems (cochlea, retina, and vestibular apparatus, respectively) are more affected than their central nervous system connections and processes.

Cognitive function and motor control are two more nervous system functions that are affected by the ageing process as can be readily observed in the aged population. We are characterising the genomic changes in specific populations of cells within these ageing-affected systems. For example, using state-of-the-art, laser based microdissection, we can collect midbrain dopamine neurons, which play an important role in motor control as can be appreciated from Parkinson's disease, at different ages and determine changes in mitochondrial DNA and the expression level of various genes.

Similar approaches are being used for spinal cord motor neurons and inner ear vestibular hair cells. Knowing how ageing affects the nervous system is important, but we also need to be able to intervene if we are to improve the quality of life of aged individuals. Calorie restriction, whereby the daily calorie intake is reduced by 20-40% (but without malnutrition), is the only presently known intervention that retards the ageing process, at least in animal models. We are establishing CR to determine whether the ageing-related changes we see in the various cell populations of interest are modified by this intervention. If this is the case, we will then set out to determine how CR achieves this.

Research methods used in the lab include: Animal models Laser based microdissection Immunocytochemistry RNA and DNA techniques Real-time and end-point PCR Immunofluorescence microscopy Cryosectioning


Qualifications

  • Doctor of Philosophy, University of Queensland

Keywords

  • Aging and Brain Function
  • Anatomy
  • Animal Models
  • Cell Culture Models
  • Developmental Neurobiology
  • Ergonomics
  • Gene Expression
  • Immunocytochemistry
  • Mitochondrial genomics
  • Modern Techniques
  • Molecular Biology
  • Neuroanatomy
  • Neurobiology
  • Physiology
  • Single Cell Genomics
  • Viral Vectors

Fields of Research

Code Description Percentage
060199 Biochemistry and Cell Biology not elsewhere classified 25
110399 Clinical Sciences not elsewhere classified 50
170199 Psychology not elsewhere classified 25

Professional Experience

UON Appointment

Title Organisation / Department
Senior Lecturer University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Academic appointment

Dates Title Organisation / Department
1/03/2005 - 21/06/2015 Academic University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
1/07/1997 - 1/04/2004 Research Scientist University of California, San Diego
Department of Pediatrics, School of Medicine UCSD
United States

Awards

Research Award

Year Award
1995 CJ Martin Fellowship
Unknown
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (38 outputs)

Year Citation Altmetrics Link
2015 McIlroy DJ, Bigland M, White AE, Hardy BM, Lott N, Smith DW, Balogh ZJ, 'Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery', JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, 78 282-288 (2015) [C1]
DOI 10.1097/TA.0000000000000519
Citations Scopus - 4Web of Science - 3
Co-authors Zsolt Balogh
2015 Quinn RK, Brown AL, Goldie BJ, Levi EM, Dickson PW, Smith DW, et al., 'Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats', Translational Psychiatry, 5 (2015) [C1]

Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that a... [more]

Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that addiction/relapse vulnerability was associated with deficits in synaptic plasticityassociated gene expression in the dorsal striatum (DS). Notable was the strong reduction in expression for activity-regulated cytoskeleton-associated protein (Arc) considered a master regulator of synaptic plasticity. In the present study, we confirmed that Arc messenger RNA was significantly decreased in the DS, but importantly, we identified that this reduction was restricted to the dorsomedial (DMS) and not dorsolateral striatum (DLS). There is recent evidence of microRNA (miRNA)-associated posttranscriptional suppression of Arc and animal models of addiction have identified a key role for miRNA in the regulation of addiction-relevant genes. In further support of this link, we identified several differentially expressed miRNA with the potential to influence addiction-relevant plasticity genes, including Arc. A key study recently reported that miR-212 expression is protective against compulsive cocaine-seeking. Supporting this hypothesis, we found that miR-212 expression was significantly reduced in the DMS but not DLS of addiction-vulnerable animals. Together, our data provide strong evidence that miRNA promote ongoing plasticity deficits in the DS of addiction-vulnerable animals.

DOI 10.1038/tp.2014.144
Citations Scopus - 2
Co-authors Murray Cairns, Christopher Dayas, Phil Dickson
2015 Murray HC, Maltby VE, Smith DW, Bowden NA, 'Nucleotide excision repair deficiency in melanoma in response to UVA.', Exp Hematol Oncol, 5 6 (2015)
DOI 10.1186/s40164-016-0035-4
Co-authors Nikola Bowden, Vicki E Maltby
2015 Parkinson GM, Dayas CV, Smith DW, 'Age-related gene expression changes in substantia nigra dopamine neurons of the rat.', Mech Ageing Dev, 149 41-49 (2015) [C1]
DOI 10.1016/j.mad.2015.06.002
Co-authors Christopher Dayas
2015 Thomas J, Garg ML, Smith DW, 'Effects of dietary supplementation with docosahexaenoic acid (DHA) on hippocampal gene expression in streptozotocin induced diabetic C57Bl/6 mice', Journal of Nutrition and Intermediary Metabolism, 2 2-7 (2015) [C1]

© 2015 The Authors. A body of evidence has accumulated indicating diabetes is associated with cognitive impairments. Effective strategies are therefore needed that will delay or ... [more]

© 2015 The Authors. A body of evidence has accumulated indicating diabetes is associated with cognitive impairments. Effective strategies are therefore needed that will delay or prevent the onset of these diabetes-related deficits. In this regard, dietary modification with the naturally occurring compound, docosahexaenoic acid (DHA), holds significant promise as it has been shown to have anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The hippocampus, a limbic structure involved in cognitive functions such as memory formation, is particularly vulnerable to the neurotoxic effects related to diabetes, and we have previously shown that streptozotocin-induced diabetes alters hippocampal gene expression, including genes involved in synaptic plasticity and neurogenesis. In the present study, we explored the effects of dietary supplementation with DHA on hippocampal gene expression in C57Bl/6 diabetic mice. Diabetes was established using streptozotocin (STZ) and once stable, the dietary intervention group received AIN93G diet supplemented with DHA (50 mg/kg/day) for 6 weeks. Microarray based genome-wide expression analysis was carried out on the hippocampus of DHA supplemented diabetic mice and confirmed by real time polymerase chain reaction (RT-qPCR). Genome-wide analysis identified 353 differentially expressed genes compared to non-supplemented diabetic mice. For example, six weeks of dietary DHA supplementation resulted in increased hippocampal expression of Igf II and Sirt1 and decreased expression of Tnf-a, Il6, Mapkapk2 and ApoE, compared to non-supplemented diabetic mice. Overall, DHA supplementation appears to alter hippocampal gene expression in a way that is consistent with it being neuroprotective in the context of the metabolic and inflammatory insults associated with diabetes.

DOI 10.1016/j.jnim.2015.04.001
Co-authors Manohar Garg
2014 James MH, Quinn RK, Ong LK, Levi EM, Charnley JL, Smith DW, et al., 'mTORC1 inhibition in the nucleus accumbens 'protects' against the expression of drug seeking and 'relapse' and is associated with reductions in GluA1 AMPAR and CAMKIIa levels.', Neuropsychopharmacology, 39 1694-1702 (2014) [C1]
DOI 10.1038/npp.2014.16
Citations Scopus - 4Web of Science - 1
Co-authors Christopher Dayas, Linkooi Ong, Phil Dickson
2014 McIlroy DJ, Jarnicki AG, Au GG, Lott N, Smith DW, Hansbro PM, Balogh ZJ, 'Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery', Journal of Critical Care, 29 1133.e1-1133.e5 (2014) [C1]

© 2014 The Authors. Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed ... [more]

© 2014 The Authors. Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component. Methods: Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition. Results: Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component. Conclusions: Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.

DOI 10.1016/j.jcrc.2014.07.013
Citations Scopus - 5
Co-authors Philip Hansbro, Gough Au, Zsolt Balogh
2014 Thomas J, Garg ML, Smith DW, 'Dietary resveratrol supplementation normalizes gene expression in the hippocampus of streptozotocin-induced diabetic C57Bl/6 mice', Journal of Nutritional Biochemistry, 25 313-318 (2014) [C1]

Diabetes is associated with cognitive impairment and brain aging, with alterations in hippocampal neurogenesis and synaptic plasticity implicated in these changes. As the prevalen... [more]

Diabetes is associated with cognitive impairment and brain aging, with alterations in hippocampal neurogenesis and synaptic plasticity implicated in these changes. As the prevalence of diabetes continues to rise, readily implemented strategies are increasingly needed in order to protect the brain's cognitive functions. One possibility is resveratrol (RES) (3,5,4- trihydroxystilbene), a polyphenol of the phytoalexin family that has been shown to be protective in a number of neuropathology paradigms. In the present study, we sought to determine whether dietary supplementation with RES has potential for the protection of cognitive functions in diabetes. Diabetes was induced using streptozotocin, and once stable, animals received AIN93G rodent diet supplemented with RES for 6 weeks. Genome-wide expression analysis was conducted on the hippocampus and genes of interest were confirmed by quantitative, real-time polymerase chain reaction. Genome-wide gene expression analysis of the hippocampus revealed that RES supplementation of the diabetic group resulted in 481differentially expressed genes compared to non-supplemented diabetic mice. Intriguingly, gene expression that was previously found significantly altered in the hippocampus of diabetic mice, and that is implicated in neurogenesis and synaptic plasticity (Hdac4, Hat1, Wnt7a, ApoE), was normalized following RES supplementation. In addition, pathway analysis revealed Jak-Stat signaling was the most significantly enriched pathway. The Jak-Stat pathway induces a pro-inflammatory signaling cascade, and we found most genes involved in this cascade (e.g. Il15, Il22, Socs2, Socs5) had significantly lower expression following RES supplementation. These data indicate RES could be neuroprotective and beneficial for the maintenance of cognitive function in diabetes. © 2014 Elsevier Inc.

DOI 10.1016/j.jnutbio.2013.11.005
Citations Scopus - 6Web of Science - 4
Co-authors Manohar Garg
2014 Parkinson GM, Dayas CV, Smith DW, 'Increased mitochondrial DNA deletions in substantia nigra dopamine neurons of the aged rat.', Current aging science, 7 155-160 (2014) [C2]
Citations Scopus - 1
Co-authors Christopher Dayas
2014 James MH, Campbell EJ, Walker FR, Smith DW, Richardson HN, Hodgson DM, Dayas CV, 'Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats', Frontiers in Behavioral Neuroscience, 8 (2014) [C1]
DOI 10.3389/fnbeh.2014.00244
Citations Scopus - 4Web of Science - 2
Co-authors Christopher Dayas, Rohan Walker, Deborah Hodgson
2013 Balogh ZJ, McIlroy DJ, Smith DW, Hansbro PM, 'The origin and the role of mitochondrial DNA in postinjury inflammation', Journal of Critical Care, 28 1099-1100 (2013) [C3]
DOI 10.1016/j.jcrc.2013.08.027
Citations Scopus - 3Web of Science - 2
Co-authors Philip Hansbro, Zsolt Balogh
2013 Thomas J, Garg ML, Smith DW, 'Altered expression of histone and synaptic plasticity associated genes in the hippocampus of streptozotocin-induced diabetic mice', Metabolic Brain Disease, 28 613-618 (2013) [C1]
DOI 10.1007/s11011-013-9418-y
Citations Scopus - 7Web of Science - 4
Co-authors Manohar Garg
2013 Thomas J, Garg ML, Smith DW, 'Dietary supplementation with resveratrol and/or docosahexaenoic acid alters hippocampal gene expression in adult C57Bl/6 mice', Journal of Nutritional Biochemistry, 24 1735-1740 (2013) [C1]

The hippocampus is an important brain structure for multiple cognitive functions, including memory formation. It is particularly sensitive to insults, such as stress, ischemia, an... [more]

The hippocampus is an important brain structure for multiple cognitive functions, including memory formation. It is particularly sensitive to insults, such as stress, ischemia, and aging; all of these can affect hippocampal and therefore cognitive function. To understand the potential of diet for the preservation of hippocampal function, we investigated the effects of dietary supplementation with resveratrol (RES) or docosahexaenoic acid (DHA), or their combination, on hippocampal gene expression in adult C57BL/6 mice. Animals in the supplemented group received either 50 mg/kg/day of RES or DHA, while the combination group received 50 mg/kg/day of each supplement. Dietary supplements were mixed with the AIN93G diet, and supplementation lasted 6 weeks. The control group received AIN93G diet alone for the same period. At the end of the experiment, the hippocampi were processed for genome-wide gene expression and pathway analyses. Most of the genes that were significantly altered were associated with inflammatory responses as determined by pathway analysis. RES-supplemented animals showed decreased expression of IL-6 ( P=001), MAPKapk2 ( P=015), and increased expression for PI3. KR2 ( P=034) and Wnt7a ( P=004) expression. DHA-supplemented animals showed a decreased IL-6 ( P=003) and an increased Wnt7a ( P=003) expression. Animals on the combination diet showed a decreased IL-6 ( P=005) and Apolipoprotien E ( ApoE) ( P=035) expression. Our findings demonstrate that hippocampal gene expression is significantly altered by all three dietary supplementation regimes. Moreover, our analysis indicates that RES and DHA likely exert their beneficial effects through antiinflammatory mechanisms. © 2013 Elsevier Inc.

DOI 10.1016/j.jnutbio.2013.03.002
Citations Scopus - 4Web of Science - 2
Co-authors Manohar Garg
2013 Cahif A, Parkinson GM, Dayas CV, Smith DW, 'Characterisation of mitochondrial DNA deletions by long-PCR in central nervous system regions of young, middle- and old-aged rats.', Current Aging Science, 6 232-238 (2013) [C1]
Citations Scopus - 2
Co-authors Christopher Dayas
2013 Brown AL, Day TA, Dayas CV, Smith DW, 'Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons', BIOMED RESEARCH INTERNATIONAL, (2013) [C1]
DOI 10.1155/2013/747938
Citations Scopus - 3Web of Science - 2
Co-authors Christopher Dayas
2012 Barreto RDA, Walker FR, Dunkley PR, Day TA, Smith DW, 'Fluoxetine prevents development of an early stress-related molecular signature in the rat infralimbic medial prefrontal cortex. Implications for depression?', BMC Neuroscience, 13 1-12 (2012) [C1]
Citations Scopus - 12Web of Science - 9
Co-authors Peter Dunkley, Rohan Walker
2012 Dayas CV, Smith DW, Dunkley PR, 'An emerging role for the mammalian Target of Rapamycin (mTOR) in 'pathological' protein translation: Relevance to cocaine addiction', Frontiers in Pharmacology, 3 1-12 (2012) [C1]
Citations Scopus - 11Web of Science - 7
Co-authors Peter Dunkley, Christopher Dayas
2011 James MH, Charnley JL, Flynn JR, Smith DW, Dayas CV, 'Propensity to 'relapse' following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei', Neuroscience, 199 235-242 (2011) [C1]
Citations Scopus - 24Web of Science - 21
Co-authors Christopher Dayas
2011 James MH, Charnley JL, Levi EM, Jones E, Yeoh JW, Smith DW, Dayas CV, 'Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking', International Journal of Neuropsychopharmacology, 14 684-690 (2011) [C1]
DOI 10.1017/s1461145711000423
Citations Scopus - 51Web of Science - 43
Co-authors Christopher Dayas
2011 Brown AL, Flynn JR, Smith DW, Dayas CV, 'Down-regulated striatal gene expression for synaptic plasticity-associated proteins in addiction and relapse vulnerable animals', International Journal of Neuropsychopharmacology, 14 1099-1110 (2011) [C1]
Citations Scopus - 12Web of Science - 9
Co-authors Christopher Dayas
2010 James MH, Charnley JL, Jones E, Levi E, Yeoh JW, Flynn JR, et al., 'Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour', Plos One, 5 e12980 (2010) [C1]
DOI 10.1371/journal.pone.0012980
Citations Scopus - 29Web of Science - 24
Co-authors Christopher Dayas
2009 McInerny SC, Brown AL, Smith DW, 'Region-specific changes in mitochondrial D-loop in aged rat CNS', Mechanisms of Ageing and Development, 130 343-349 (2009) [C1]
DOI 10.1016/j.mad.2009.01.008
Citations Scopus - 14Web of Science - 10
2009 Brown AL, Smith DW, 'Improved RNA preservation for immunolabeling and laser microdissection', RNA: A Publication of the RNA Society, 15 2364-2374 (2009) [C1]
DOI 10.1261/rna.1733509
Citations Scopus - 14Web of Science - 14
2007 Smith DW, Jinnah HA, 'Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice', Metabolic Brain Disease, 22 39-43 (2007) [C1]
DOI 10.1007/s11011-007-9044-7
Citations Scopus - 3Web of Science - 3
2004 Smith DW, Friedmann T, 'Discrepant effects of culture conditions on survival and function of dopaminergic neurons.', Neuroreport, 15 1025-1028 (2004) [C1]
DOI 10.1097/00001756-200404290-00018
2003 Tokumine J, Kakinohana O, Cizkova D, Smith DW, Marsala M, 'Changes in spinal GDNF, BDNF and NT-3 expression after transient spinal cord ischemia in the rat.', Neuroscience Research, 74 552-561 (2003) [C1]
DOI 10.1002/jnr.10760
2003 Smith DW, Day TA, 'Catecholamine and oxytocin cells respond to hypovolaemia as well as hypotension', Neuroreport, 14 1493-1495 (2003) [C1]
DOI 10.1097/00001756-200308060-00018
2002 Visser JE, Smith DW, Fried T, Rothstein JD, Jinnah HA, 'Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.', Brain Res Dev Brain Res, (2002) [C1]
2000 Smith D, 'Characterization of the Dopamine Defect in Primary Cultures of Dopaminergic Neurons from Hypoxanthine Phosphoribosyltransferase Knockout Mice', Molecular Therapy, 1 486-491 (2000)
DOI 10.1006/mthe.2000.0057
1999 Buller KM, Smith DW, Day TA, 'Differential recruitment of hypothalamic neuroendocrine and ventrolateral medulla catecholamine cells by non-hypotensive and hypotensive hemorrhages', BRAIN RESEARCH, 834 42-54 (1999)
DOI 10.1016/S0006-8993(99)01539-5
Citations Web of Science - 59
1999 Buller KM, Smith DW, Day TA, 'NTS catecholamine cell recruitment by hemorrhage and hypoxia', NEUROREPORT, 10 3853-3856 (1999)
DOI 10.1097/00001756-199912160-00024
Citations Web of Science - 26
1995 SMITH DW, SIBBALD J, KHANNA S, DAY TA, 'RAT VASOPRESSIN CELL RESPONSES TO SIMULATED HEMORRHAGE - STIMULUS-DEPENDENT ROLE FOR A1 NORADRENERGIC NEURONS', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 268 R1336-R1342 (1995)
Citations Web of Science - 41
1995 SMITH DW, DAY TA, 'HYPOVOLEMIC AND OSMOTIC STIMULI INDUCE DISTINCT PATTERNS OF C-FOS EXPRESSION IN THE RAT SUBFORNICAL ORGAN', BRAIN RESEARCH, 698 232-236 (1995)
DOI 10.1016/0006-8993(95)00975-V
Citations Web of Science - 22
1995 Smith DW, Buller KM, Day TA, 'Role of ventrolateral medulla catecholamine cells in hypothalamic neuroendocrine cell responses to systemic hypoxia', JOURNAL OF NEUROSCIENCE, 15 7979-7988 (1995)
Citations Web of Science - 72
1994 SMITH DW, DAY TA, 'C-FOS EXPRESSION IN HYPOTHALAMIC NEUROSECRETORY AND BRAIN-STEM CATECHOLAMINE CELLS FOLLOWING NOXIOUS SOMATIC STIMULI', NEUROSCIENCE, 58 765-775 (1994)
DOI 10.1016/0306-4522(94)90453-7
Citations Web of Science - 49
1994 KHANNA S, SIBBALD J, SMITH DW, DAY TA, 'INITIATION OF RAT VASOPRESSIN CELL RESPONSES TO SIMULATED HYPOTENSIVE HEMORRHAGE', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 267 R1142-R1149 (1994)
Citations Web of Science - 20
1993 SMITH DW, DAY TA, 'NEUROCHEMICAL IDENTIFICATION OF FOS-POSITIVE NEURONS USING 2-COLOR IMMUNOPEROXIDASE STAINING', JOURNAL OF NEUROSCIENCE METHODS, 47 73-83 (1993)
DOI 10.1016/0165-0270(93)90023-K
Citations Web of Science - 41
1992 DAY TA, SIBBALD J, SMITH DW, 'A1-NEURONS AND EXCITATORY AMINO-ACID RECEPTORS IN RAT CAUDAL MEDULLA MEDIATE VAGAL EXCITATION OF SUPRAOPTIC VASOPRESSIN CELLS', BRAIN RESEARCH, 594 244-252 (1992)
DOI 10.1016/0006-8993(92)91131-W
Citations Web of Science - 45
Show 35 more journal articles

Conference (13 outputs)

Year Citation Altmetrics Link
2015 Dickinson S, Smith K, Bigland M, Smith D, Jobling P, Graham B, 'Morphological analysis of microglial and astrocyte populations in the superficial dorsal horn of spinal cord in aged mice', JOURNAL OF NEUROCHEMISTRY (2015) [E3]
Co-authors Brett Graham, Phillip Jobling
2014 Khan SI, Hübner PP, Smith DW, Brichta AM, Migliaccio AA, 'Ageing reduces vestibulo-ocular reflex adaptation in mice J Vestib Res', Journal of Vestibular Research: Equilibrium and Orientation: an international journal of experimental and clinical vestibular science (2014) [E3]
DOI 10.3233/VES-140517
Co-authors Alan Brichta
2013 Bigland M, Parkinson G, Brichta AM, Smith DW, 'Evidence for mitochondrial DNA deletions in vestibular hair cells of the aged rat', Proceedings of the Australian Neuroscience Society (2013) [E3]
Co-authors Alan Brichta
2012 Parkinson GM, Smith DW, 'Age-related increase in mitochondrial DNA copy number in midbrain dopamine neurons of the rat', Abstracts. Australian Neuroscience Society 32nd Annual Meeting (2012) [E3]
2012 James MH, Charnley JL, Levi EM, Dunkley PR, Smith DW, Dickson PW, Dayas CV, 'A role for the mTOR pathway in the development of addiction', Abstracts. Australian Neuroscience Society 32nd Annual Meeting (2012) [E3]
Co-authors Christopher Dayas, Phil Dickson, Peter Dunkley
2012 Thomas J, Smith DW, Garg ML, 'Early molecular signature of neuro-protection in hippocampus of resveratrol diet fed C57BL/6 mice', Resveratrol 2012. 2nd International Conference of Resveratrol and Health (2012) [E3]
Co-authors Manohar Garg
2012 Brown AL, Flynn JR, Dayas CV, Smith DW, 'Altered gene expression in cell signalling pathways of midbrain dopamine neurons from addiction and relapse vulnerable animals', Drug and Alcohol Review: Abstracts of the Australasian Professional Society on Alcohol and other Drugs Conference 2012 (2012) [E3]
Co-authors Christopher Dayas
2012 Dayas CV, Quinn RK, Goldie BJ, Brown AM, Levi EM, Smith DW, Cairns MJ, 'Association of miRNAs with addiction-relevant synaptic plasticity genes', Abstract Book. Biological Psychiatry Australia Scientific Meeting (2012) [E3]
Co-authors Christopher Dayas, Murray Cairns
2011 Thomas J, Smith DW, Garg ML, 'Dietary supplementation with resveratrol normalizes histone deacetylase (HDAC4) in the hippocampus of streptozotocin-induced diabetic mice', Australasian Medical Journal (2011) [E3]
Co-authors Manohar Garg
2011 Barreto RDA, Walker FR, Dunkley PR, Day TA, Smith DW, 'Alteration of neurotrophic factor pathway gene expression in the rat infralimbic medial prefrontal cortex by subchronic restraint stress is reversed by fluoxetine', Posters. Australian Neuroscience Society 31st Annual Meeting (2011) [E3]
Co-authors Peter Dunkley, Rohan Walker
2010 Thomas J, Smith DW, Garg ML, 'Dietary supplementation with resveratrol reduces erythrocyte arachidonic and docosahexaenoic acids levels in diabetic mice', Proceedings of the Nutrition Society of Australia (2010) [E3]
Co-authors Manohar Garg
2007 McInerny SC, Brown AL, Smith DW, 'Brain region-specific decrease in mitochondrial D-loop in aged rats (Poster)', 7th IBRO 2007 World Congress of Neuroscience Program (2007) [E3]
1995 Day TA, Smith DW, Buller KM, 'Regulation of neurosecretory cell activity by A1 noradrenergic neurons', 1st Joint World Congress of Neurohypophysis and Vasopressin (1995)
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Grants and Funding

Summary

Number of grants 17
Total funding $4,789,925

Click on a grant title below to expand the full details for that specific grant.


20152 grants / $45,000

Maintaining our cognitive abilities as we grow old: preventing the effects of ageing on the brain$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Doug Smith, Doctor Frederick Walker
Scheme Project Grant
Role Lead
Funding Start 2015
Funding Finish 2015
GNo G1500078
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

Dizzy and Deaf - restoring signals from the inner ear$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Rebecca Lim, Professor Alan Brichta, Professor Robert Callister, Doctor Doug Smith
Scheme Project Grant
Role Investigator
Funding Start 2015
Funding Finish 2015
GNo G1501395
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20131 grants / $35,000

20122 grants / $313,375

The effects of ageing on the peripheral vestibular system. Can ageing-related functional decline be reduced or prevented?$298,375

Funding body: Garnett Passe and Rodney Williams Memorial Foundation

Funding body Garnett Passe and Rodney Williams Memorial Foundation
Project Team Doctor Doug Smith
Scheme Project Grant
Role Lead
Funding Start 2012
Funding Finish 2014
GNo G1100935
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON Y

2011 Emerging Research Leaders Program$15,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Doug Smith
Scheme Emerging Research Leaders Program
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1200307
Type Of Funding Internal
Category INTE
UON Y

20111 grants / $25,000

Brain Mechanisms Conferring Psychostimulant Addiction$25,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Associate Professor Chris Dayas, Emeritus Professor Peter Dunkley, Doctor Doug Smith
Scheme Near Miss Grant
Role Investigator
Funding Start 2011
Funding Finish 2011
GNo G1001052
Type Of Funding Internal
Category INTE
UON Y

20104 grants / $649,000

Laser microdissection microscopy system for cell and development biology$350,000

Funding body: ARC (Australian Research Council)

Funding body ARC (Australian Research Council)
Project Team Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Laureate Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Doctor Doug Smith, Associate Professor David McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Associate Professor Brett Graham, Associate Professor Paul Tooney, Professor Roger Smith, Laureate Professor Paul Foster, Professor Trevor Day, Professor Robert Callister
Scheme Linkage Infrastructure Equipment & Facilities (LIEF)
Role Investigator
Funding Start 2010
Funding Finish 2010
GNo G0190369
Type Of Funding Scheme excluded from IGS
Category EXCL
UON Y

ABI 7500 Real Time PCR System $34,000

Funding body: NHMRC (National Health & Medical Research Council)

20081 grants / $538,500

Dopamine mechanisms conferring resilience to depression: A new antidepressant target$538,500

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Trevor Day, Emeritus Professor Peter Dunkley, Professor David Pow, Doctor Doug Smith
Scheme Project Grant
Role Investigator
Funding Start 2008
Funding Finish 2010
GNo G0187604
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

20072 grants / $40,000

Vulnerability to depression: the role of dopamine pathways$20,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Trevor Day, Emeritus Professor Peter Dunkley, Doctor Doug Smith, Professor David Pow
Scheme Near Miss Grant
Role Investigator
Funding Start 2007
Funding Finish 2007
GNo G0187196
Type Of Funding Internal
Category INTE
UON Y

Characterisation of the brain mechanisms linking vulnerability to stress and vulnerability to drug addiction$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Trevor Day, Associate Professor Chris Dayas, Doctor Doug Smith
Scheme Project Grant
Role Investigator
Funding Start 2007
Funding Finish 2007
GNo G0187255
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

20042 grants / $13,679

Characterisation of age-related gene expression changes in midbrain dopamine neurons$12,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Doug Smith
Scheme New Staff Grant
Role Lead
Funding Start 2004
Funding Finish 2004
GNo G0184998
Type Of Funding Internal
Category INTE
UON Y

Society for Neuroscience Annual Meeting, 23-27 October 2004$1,679

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Doug Smith
Scheme Travel Grant
Role Lead
Funding Start 2004
Funding Finish 2004
GNo G0184814
Type Of Funding Internal
Category INTE
UON Y

20031 grants / $2,489,371

Genetic aberrations in HPRT deficiency$2,489,371

Funding body: National Institute of Neurological Disorders (NIH)

Funding body National Institute of Neurological Disorders (NIH)
Project Team

Theodore Friedmann

Scheme Project
Role Investigator
Funding Start 2003
Funding Finish 2007
GNo
Type Of Funding External
Category EXTE
UON N

20011 grants / $641,000

Array screening for Lesch-Nyhan disese$641,000

Funding body: NICH (NIH)

Funding body NICH (NIH)
Project Team

Theodore Friedmann

Scheme R21
Role Investigator
Funding Start 2001
Funding Finish 2003
GNo
Type Of Funding External
Category EXTE
UON N
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Research Supervision

Number of supervisions

Completed6
Current5

Total current UON EFTSL

PhD2.05

Current Supervision

Commenced Level of Study Research Title / Program / Supervisor Type
2015 PhD Spinal Cord Glial Changes in Pain
PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2012 PhD Ageing of the Inner Ear Balance System
PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
2012 PhD The Role of Mitochondrial DNA in the Post-Injury "Inflammatory" Response Following Major Trauma
PhD (Medicine), Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2011 PhD Ageing of the Somatic Motor Nervous System: A Nuclear and Mitochondrial Genome Perspective
PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
2007 PhD Role of dopamine in depression
Medical Science, University of Newcastle
Principal Supervisor

Past Supervision

Year Level of Study Research Title / Program / Supervisor Type
2015 Masters Nucleotide Excision Repair of UVA-Induced DNA Damage: Regulation in Sunlight-Induced Melanoma
M Philosophy (Medical Genetic), Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2014 PhD The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) and Orexin in Drug-Seeking and Addiction-Related Behaviours
PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2013 PhD Effects of Anti-Inflammatory Bioactives on Diabetes-Induced Changes in Cognition-Related Gene Expression in the Hippocampus
PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2012 PhD Molecular Correlates of Dopamine Signalling in Addiction Vulnerability
PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
2012 PhD Dopaminergic Pathway Imbalance in the Neurobiology of Depression
PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
2006 Honours Role of mitochondrial D-loop in aging brain
Medical Science, University of Newcastle
Principal Supervisor
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Dr Doug Smith

Position

Senior Lecturer
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Focus area

Anatomy

Contact Details

Email douglas.smith@newcastle.edu.au
Phone (02) 4921 7108
Fax (02) 4921 8667

Office

Room MS306B
Building Medical Sciences
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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