Zane Andrews, PhD

Monash Research Fellow - Department of Physiology

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Qualifications

1998, BSc(Hons), University of Otago, Department of Anatomy and Structural Biology

2003, PhD, University of Otago, Department of Anatomy and Structural Biology

2004-2006 Postdoctoral Associate, Yale University, New Haven, Connecticut, USA

2006-2008 New Zealand Foundation for Research Science and Technology Postdoctoral Fellow, Yale University, New Haven, Connecticut, USA

2008-2013 Monash Fellow, Monash University, Australia

Research Interests

There are 2 fundamental questions explored in this lab;

How do metabolic hormones and/or different physiological states affect food intake and body weight regulation in the hypothalamus?

How do metabolic hormones and/or different physiological states influence neurodegenerative processes?

We are developing novel transgenic mouse lines using the cre/lox as well as cell culture techniques to explore these highly interesting questions.

The lab focuses on ghrelin, as it is an important metabolic hormone secreted from the stomach during negative energy balance (a metabolic state producing hunger) that drives food intake and body weight gain. Ghrelin-induced food intake is primarily mediated via hypothalamic feeding circuits and current research in the lab focuses on the mechanisms regulating hypothalamic responsiveness to peripheral metabolic hormones such as ghrelin. Recently, we reported that ghrelin activates mitochondrial function, which plays an integral role in maintaining hypothalamic responsiveness to circulating ghrelin. Understanding the interactions between metabolic hormones and hypothalamic mitochondrial function is a core focus of the lab. Current projects involve selectively knocking out mitochondrial proteins in feeding neurons of the hypothalamus and examining the resulting outcome using metabolic phenotyping, molecular biology and in vivo physiology. 

In addition, metabolic hormones such as ghrelin act outside the hypothalamus in other regions of the brain including the hippocampus and midbrain. Interestingly, ghrelin produces similar mitochondrial changes in the midbrain that confers neuroprotection in models of Parkinson’s disease. Understanding exactly how ghrelin regulates mitochondrial function and neuroprotection in models of Parkinson’s disease is the second core focus of the lab.

Studies in this lab open the door to an unexplored avenue of metabolic neuroscience pertaining to the regulation of neurodegeneration by hormones that control energy metabolism and body weight regulation. The importance of this emerging field is underscored by recent epidemiological reports showing that obesity, diabetes and elevated body mass index predispose to future risk of Parkinson’s disease, suggesting that perturbations in energy metabolism resulting in obesity not only affect pathological conditions such as cancer, diabetes and heart disease, but also neurodegeneration. Moreover, the obesity epidemic has exploded in recent years and given that neurological disease takes many years to manifest into observable symptoms, it is reasonable to assume that an increase in the prevalence of neurological disease as the result of profound long term obesity may occur in the near future.

Recently this work has received a lot of public interest with features in popular science magazines such as Scientific American and Australasian Science as well as Reader’s Digest.

Current Projects Available for Students

Ghrelin-induced neuroprotection is mediated by AMPK

Obesity affects neurodegeneration by through mitochondrial dysfunction

Metabolic regulation of neurogenesis in the brain

Publications

Andrews ZB, Erion DM, Zigman J, Elsworth J, Savitt JM, Tschoep M, Elmquist JK, Sleeman MW, Roth R, Horvath TL. Ghrelin promotes nigrostriatal dopamine function and protects dopamine cells in a mouse model of Parkinson’s disease. Submitted PNAS.

Andrews ZB, Horvath TL. Uncoupling Protein-2 mediates lifespan in mice by regulating reactive oxygen species.  American Journal of Physiology Endocrinology and metabolism, 2009 296(4):E621-7.

Horvath TL, Andrews ZB, Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends in Endocrinology and Metabolism, 2009 20 (2): 78-87.

Dietrich MO, Andrews ZB, Horvath, TL. Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaption. Journal of Neuroscience, 2008 Oct 15;28(42):10766-71. Impact factor = 7.49

Andrews ZB, , Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL Diano S. Uncoupling protein-2 mediates ghrelin’s action on NPY/AgRP neurons. Nature,  2008 454(7206): 846-51. 

Andrews ZB, Horvath TL. Tastleless food reward. Neuron 2008 57 806-808.

Coppola A, Zhong Wu L, Andrews ZB, Roy MC, Gao Q, Pinto S, Friedman JM, Galton V, Ricquier D, Richard D, Horvath TL, Gao XB, Sabrina Diano. Role of arcuate glial-neuronal interplay in feeding regulation. Cell Metabolism 2007 (1) 21-33.

Abizaid A, Zhong-Wu, Andrews ZB, Elsworth JD, Roth RH, Sleeman M, Mineur YS, Gao XB, Picciotto MR, Tschöp M, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal of Clinical Investigation, 2006 116(12):3229-3239.

Andrews ZB, Rivera A, Elsworth JD, Roth RH, Agnati L, Gago B, Abizaid A, Schwartz M, Fuxe K, Horvath TL. Uncoupling protein 2 promotes nigrostriatal dopamine neuronal function. European Journal of Neuroscience, 2006 24:32-36.

Andrews ZB, Zhoa H, Frugier T, Meguro R, Grattan DR, Koishi K, McLennan IS. Transforming growth factor beta 2 haploinsufficient mice develop age-related nigrostriatal dopamine deficits. Neurobiology of Disease, 2006 21 (3): 568-575.

Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the CNS: In support of function and survival. Nature Reviews Neuroscience, 2005 6(11):829-40.

McGeachie AB, Koishi K, Andrews ZB, McLennan IS. Analysis of mRNAs that are enriched in the post-synaptic domain of the neuromuscular junction. Molecular and Cellular Neuroscience 2005 30(2):173-85

Andrews ZB. Neuroendocrine regulation of prolactin secretion during late pregnancy: easing the transition into lactation. Journal of Neuroendocrinology. 2005 17(7):466-73.

Conti B, Sugama S, Lucero J, Winsky-Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, Sanna PP, Horvath T, Bartfai T. Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity. Journal of Neurochemistry 2005 93(2):493-501.

Andrews ZB, Horvath B, Barnstable CJ, Elsworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL. Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson's disease. Journal of Neuroscience. 2005 25(1):184-91.

Andrews ZB and Grattan DR. Opioid receptor regulation of prolactin secretion during pregnancy and lactation. Journal of Neuroendocrinology 15, 227-36 (2003).

Augustine RA, Kokay IC, Andrews ZB, Ladyman SR, Grattan DR. Quantitation of prolactin receptor mRNA in the maternal rat brain during pregnancy and lactation. Journal of  Molecular Endocrinology 2003 31(1):221-3.

Andrews ZB and Grattan DR. Opioid receptor regulation of prolactin secretion during pregnancy and lactation. Journal of Neuroendocrinology 15, 227-36 (2003).

Andrews ZB, Grattan DR. Opioid control of prolactin secretion in late pregnant rats is mediated by tuberoinfundibular neurons. Neuroscience Letters  328, 60-64 (2002).

Grattan DR, Pi XJ, Andrews ZB, Augustine R, Kokay IC, Summerfield M, Todd B, Bunn SJ. Prolactin Receptors in the brain during pregnancy and lactation: Implications for behaviour. Hormones and Behavior  40, 115-124 (2001).

Andrews ZB, Kokay IC and Grattan DR. Dissociation of prolactin secretion from tuberoinfundibular dopamine activity in late pregnant rats. Endocrinology 142, 2719-2724 (2001).