Professor David Spanswick
Professor - Department of Physiology
BSc (Hons), M.Sc, PhD
Department of Physiology,
Monash University VIC 3800 Australia
26 Innovation Walk, Room F206 (Physiology - Bld 13F)
Tel: +61 3 990 24307
Fax: +61 3 990 20707
Dave Spanswick graduated from University of East Anglia, UK in 1986 (B.Sc).
He then obtained his PhD at University of Birmingham, studying neurophysiology. He remained in Birmingham as a Post-doctoral research fellow in Steve Logan’s group before moving to work in Canada with Leo Renaud’s group and Japan with Syogoro Nishi, Hideho Higashi, Hiroe Inokuchi and Megumu Yoshimura. He subsequently returned to the UK as a lecturer in the Department of Biomedical Sciences, University of Aberdeen before taking a sabbatical at the Department of Pharmacology, University of Cambridge and Parke-Davis. He was appointed a senior lecturer, University of Warwick in 2000 and Professor of Molecular Neuroscience at Warwick Medical School in 2004. He arrived at the Department of Physiology, Monash University in October 2011.
The long-term aim of our research is to address questions relating to the mechanisms by which neuroendocrine, autonomic and behavioural responses to disturbances in energy levels are integrated, and to identify and isolate the component parts at the cellular level that underpin this behaviour. Thus we seek to understand and identify central neural cellular mechanisms contributing to the development and manifestation of obesity and the associated co-morbidities, diabetes and hypertension. Previous research undertaken by the group has focused on the central integration of nutrient, hormone and neuropeptide signals in key hypothalamic and spinal areas involved in regulating food intake and energy homeostasis. Maintaining and co-ordinating energy balance is a function of specific key areas of the brain which act to integrate information regarding the energy status of the body and formulate appropriate responses to maintain energy balance. Dysfunction or disruption to these signalling mechanisms manifests as pathophysiological states. Through an understanding of central neural cellular and molecular signalling mechanisms of nerve cells and circuits engaged in maintaining energy homeostasis we seek to investigate:
- The central neural mechanisms controlling energy balance, how they change with age and contribute to the development of obesity and diabetes.
- Glucose-sensing neural circuits, the mechanisms by which neurones detect changes in glucose levels and the age- and energy status-dependent plasticity associated with these neurones and circuits.
- The role of epigenetics in hypothalamic neuronal plasticity and obesity
- The impact of protein and fermentable carbohydrate diets on the functional operation of neural circuits controlling energy balance.
- The role of the gut flora in the development of energy status-sensing neural circuits, diabetes and obesity.
- Central neural aspects linking obesity and hypertension: a focus on spinal sympathetic neural circuits and signalling pathways.
To address these issues we have developed key strategic collaborations and partnerships, both nationally and internationally to ensure a multidisciplinary approach spanning the sub-cellular genetic, through isolated tissue approaches to whole organism physiology and pathophysiology.
Age and energy status-dependent plasticity of glucose sensing neural circuits in the hypothalamus
This study aims to identify the signal transduction mechanisms employed by glucose-sensing neurones and associated neural circuits in the hypothalamus and how they change depending on the age and energy status of the organism. The signaling pathways underlying the long-term modulation of the functional operation of these key glucose-sensing circuits could lead to novel targets and strategies for therapeutic intervention into diabetes.
Spinal sympathetic preganglionic neurones and the development of hypertension: a role for nitric oxide and electrical synapses
The causes of primary or essential hypertension are largely unknown. However early stages are characterized by overactive or enhanced sympathetic autonomic responsiveness. Thus disruption of the molecular mechanisms and pathways regulating sympathetic neurone excitability could be important in the development and expression of conditions of autonomic dysfunction such as hypertension. Recent work in the lab revealed that nitric oxide (NO) is tonically released in, and exerts a powerful inhibitory influence on, spinal sympathetic neurones. These spinal sympathetic preganglionic neurones (SPN) are directly interconnected via electrical synapses which in turn facilitate highly synchronised rhythmic activity in these neurones. This project seeks to identify the signalling mechanisms underlying NO release in these neurones, the role of electrical synapses in this process, the mechanisms by which NO-dependent signalling is subject to regulation with age and the development of obesity and if disruption or dysfunction of this pathway contributes to the development and manifestation of hypertension.
Current Lab Members
Dr Natalie Michael - Post Doctoral Researcher
Feb, 1999 Joy Chrisholm Fellowship: awarded by The Epilepsy Research Foundation.
July, 1998 William Ramsay Henderson Trust Scholarship.
July, 1998 Royal Society Travel Scholarship
May 1995 Royal Society Travel Scholarship
May 1993 Royal Society Travel Scholarship
Feb 1993 Canadian Heart & Stroke Foundation Research Fellowship.
- Referee for Journals: Nature, Journal of Neuroscience, Neuropharmacology, Journal of Physiology; Journal of Neurophysiology; Neuroscience Letters; Brain Research; Nature Neuroscience, Neuroscience; J. Neurosci., Methods; Cell Metabolism; Neuropharmacology; Trends in Endocrinology & Metabolism; Biological Psychiatry
- Referee for Grant Awarding Agencies: The Wellcome Trust; British Heart Foundation; BBSRC; MRC; Canadian Institutes for Health Research (CIHR); NIH; NHS
- PhD External Examiner: University of Manchester, University of Cambridge, Imperial College, London, University of Ottawa
- PhD Co-supervisor for Students at University of Ottawa Canada
- CSO and founder of Neurosolutions Ltd.
- Chief Scientific Officer (Co-Founder) of Cerebrasol Ltd, UK and Montreal, Canada.
- Director and Co-founder of Kamelion.
- Consultant Scientist for GSK, Eli-Lilly, Neurotherapeutics (US), Envivo Pharmaceuticals (US) and Envoytherapeutics (US).
Selected and Recent Publications
Jeggoa, R, Zhao, F, Spanswick, D. Electrophysiological Techniques for Studying Synaptic Activity In Vivo. Current Protocols in Pharmacology (2014): 11-11.
Zhao, F, Jeggoa, R, Weia, H, Whyment, A, Fanga, X, Spanswick, D,. (2014) In vivo electrophysiological recording techniques for the study of neuropathic pain in rodent models. Current Protocols in Pharmacology (In Press)
Lado WE, Spanswick DC, Lewis JE, Trudeau VL. (2014). Electrophysiological characterization of male goldfish (Carassius auratus) ventral preoptic area neurons receiving olfactory inputs. Front Neurosci; 2014 Jun 30;8:185
Sleeman MW, Spanswick DC. (2014). Starving for ghrelin. Cell Metab; 2014 Jul 1;20(1):1-2
O'Hare E, Scopes DI, Kim EM, Palmer P, Spanswick D, McMahon B, Amijee H, Nerou E, Treherne JM, Jeggo R. (2014). Novel 5-aryloxypyrimidine SEN1576 as a candidate for the treatment of Alzheimer's disease. Int J Neuropsychopharmacol; 2014 Jan;17(1):117-26
Verdoorn, T., Zhao, F., Whyment, A., Morton, K., Wei, H., Fang, X., Jeggo, R., Spanswick, D., Wanaski, S., Collins, S. (2013). NP260, a novel GABA-A receptor antagonist, dampens neuronal hyperexcitability and relieves mechanical allodynia in a rat model of neuropathic pain. The Journal of Pain; (Suppl.) 14(4):S69.
O'Hare E, Scopes DI, Kim EM, Palmer P, Jones M, Whyment AD, Spanswick D, Amijee H, Nerou E, McMahon B, Treherne JM, Jeggo R. (2012). Orally bioavailable small molecule drug protects memory in Alzheimer's disease models. Neurobiol Ageing. 2013; 34(4): 1116-25.
Amijee H, Bate C, Williams A, Virdee J, Jeggo R, Spanswick D, Scopes DI, Treherne JM, Mazzitelli S, Chawner R, Eyers CE, Doig AJ. (2012). The N-methylated peptide SEN304 powerfully inhibits Aβ(1-42) toxicity by perturbing oligomer formation. Biochemistry, In Press.
Scopes DI, O'Hare E, Jeggo R, Whyment AD, Spanswick D, Kim EM, Gannon J, Amijee H, Treherne JM. (2012). Aβ oligomer toxicity inhibitor protects memory in models of synaptic toxicity. Br J Pharmacol, In Press.
Spanswick DC, Simonds SE, Cowley MA. (2012). Transmitter time: synaptic plasticity and metabolic memory in the hypothalamus. Cell Metab, In Press.
Bursi, R., Erdemli, G., Campbell, R., Hutmacher, M., Kerbusch, T., Spanswick, D., Jeggo, R., Nations, K.R., Dogterom, P., Schipper, J. and Mohammed Shahid, M. (2011). Translational PK-PD modeling of molecular target modulation for the AMPA receptor positive allosteric modulator Org26576. Psychopharmacology, In Press
Whyment AD, Coderre E, Wilson JM, Renaud LP, O'Hare E, Spanswick D. (2011) Electrophysiological, pharmacological and molecular profile of the transient outward rectifying conductance in rat sympathetic preganglionic neurons in vitro. Neuroscience, 178: 68-81.
O'Hare E, Scopes DI, Treherne JM, Norwood K, Spanswick D, Kim EM. (2010) RS-0406 Arrests Amyloid-beta Oligomer-Induced Behavioural Deterioration In Vivo. Behav Brain Res. 210(1):32-7.
Kim EM, Quinn JG, Spanswick D, O'Hare E. (2009). Feeding association between the nucleus of the solitary tract and the ventral tegmental area.
Barrett P, van den Top M, Wilson D, Mercer JG, Song CK, Bartness TJ, Morgan PJ, Spanswick D. (2009). Short Photoperiod Induced Decrease of
Histamine H3 Receptors Facilitates Activation of Hypothalamic Neurons in the Siberian Hamster. Endocrinology 150(8): 3655-3663.
Pattaranit R, van den Berg HA, Spanswick D. (2008). The development of insulin resistance in Type 2 diabetes: insights from knockout studies. Sci Prog., 2008;91(Pt 3):285-316.
van den Top, M.; Lyons, D. J.; Lee, K.; Coderre, E.; Renaud, L. P.; Spanswick, D. (2007) Pharmacological and molecular characterization of ATP-sensitive K(+) conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus Neuroscience 144 (3): 815-24
van Den Top, M., Lee, K., Whyment, A., Blanks, A and Spanswick, D. (2004). Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus. Nature Neuroscience 7 (5): 493-494
Spanswick, D. & Lee, K. (2003). Emerging anti-obesity drugs. Expert Opinion on Emerging Drugs 8(1): 217-237.
van Den Top, M., Nolan, M.F., Lee, K., Richardson, P.J. & Spanswick, D. (2003). Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones. Journal of Physiology 549(Pt 3):809-21.
Wilson, J.M., Coderre, E., Renaud, L.P. & Spanswick, D. (2002). Active and passive membrane properties of rat sympathetic preganglionic neurones innervating the adrenal medulla. Journal of Physiology 545: 945-60.
Spanswick, D., Smith, M.A., Mirshamsi, S, Routh, V.H. and Ashford, M.L.J. (2000). Insulin activates ATP-sensitive potassium channels in hypothalamic neurones of lean, but not obese rats. Nature Neuroscience 3(8):757-758.
Nolan, M.F., Logan, S.D. & Spanswick, D. (1999). Electrophysiological properties of electrical synapses between rat sympathetic preganglionic neurones in vitro. J. Physiol., 519: 753-764.
Spanswick, D., Smith, M.A., Groppi, V.E., Logan, S.D. and Ashford, M.L.J. (1997). Leptin inhibits hypothalamic neurones by activation of ATP-sensitive potassium channels. Nature, 390: 521-525.