Professor Perry Bartlett’s laboratory is focussed on understanding the mechanisms that regulate the production and function of new neurons, generated from the resident population of stem/precursor cells in a region of the adult brain known as the hippocampus. This process, called neurogenesis, declines with age, and this loss of new neurons has been associated with impairments in cognitive function as well as mood. The group has discovered that the majority of these stem cells are quiescent, but that they can be activated by stimuli as diverse as physical exercise, antidepressants, and learning.
The Bartlett group is now focussed on identifying the molecular mechanisms that regulate stem cell activation, and on using this knowledge to enhance neurogenesis and ameliorate functional deficits in mouse models of ageing dementia, stroke, anxiety and depression.
In a study that was featured on the front cover of the Journal of Neuroscience (Jhaveri et al.), the Bartlett laboratory reported development of a new cell-sorting method to purify, for the first time, hippocampal stem precursor cells to near homogeneity. The study examined the responsiveness of individual precursors to various stimuli and provided the first evidence for the presence of two distinct subpopulations of quiescent precursors in the hippocampus. The study further showed that these distinct precursors are located in different regions of the hippocampus and generate neuronal progeny that are molecularly different. Since it has been shown that neurons regulating spatial learning and those regulating anxiety and mood are located in different areas of the hippocampus, it suggests that it is the preferential activation of one of the two distinct precursor populations that may underpin the different functions of the hippocampus.
Yeshurun, Shlomo, Short, Annabel K., Bredy, Timothy W., Pang, Terence Y. and Hannan, Anthony J. (2017) Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes.Psychoneuroendocrinology, 77 225-235. doi:10.1016/j.psyneuen.2016.11.013
Ratnu, Vikram S., Emami, Michael R. and Bredy, Timothy W. (2017) Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain. Journal of Neuroscience Research, 95 1-2: 301-310. doi:10.1002/jnr.23886
Nainar, Sarah, Marshall, Paul R., Tyler, Christina R., Spitale, Robert C. and Bredy, Timothy W. (2016) Evolving insights into RNA modifications and their functional diversity in the brain. Nature Neuroscience, 19 10: 1292-1298. doi:10.1038/nn.4378
Viola, Thiago Wendt, Wearick-Silva, Luis Eduardo, De Azeredo, Lucas Araujo, Centeno-Silva, Anderson, Murphy, Conor, Marshall, Paul, Li, Xiang, Singewald, Nicolas, Garcia, Frederico, Bredy, Timothy W. and Grassi-Oliveira, Rodrigo (2016) Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB/c mice: the role of cortical BDNF, microRNA-212, and MeCP2. Psychopharmacology, 233 17: 3279-3288. doi:10.1007/s00213-016-4373-z
Marshall, Paul and Bredy, Timothy W. (2016) Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?. n p j Science of Learning, 16014. doi:10.1038/npjscilearn.2016.14
Widagdo, Jocelyn, Zhao, Qiong-Yi, Kempen, Marie-Jeanne, Tan, Men Chee, Ratnu, Vikram S., Wei, Wei, Leighton, Laura, Spadaro, Paola A., Edson, Janette, Anggono, Victor and Bredy, Timothy W. (2016) Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience, 36 25: 6771-6777. doi:10.1523/JNEUROSCI.4053-15.2016
Fenton, Georgina E., Halliday, David M., Mason, Rob, Bredy, Timothy W. and Stevenson, Carl W. (2016) Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex.Neurobiology of Learning and Memory, 135 66-72. doi:10.1016/j.nlm.2016.06.019
Alaghband, Yasaman, Bredy, Timothy W. and Wood, Marcelo A. (2016) The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action. Neuroscience Letters, 625 40-46. doi:10.1016/j.neulet.2016.01.023
Short, A. K., Fennell, K. A., Perreau, V. M., Fox, A., O'Bryan, M. K., Kim, J. H., Bredy, T. W., Pang, T. Y. and Hannan, A. J. (2016) Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Translational Psychiatry, 6 . doi:10.1038/tp.2016.109
Bjorge, Monica D., Hildrestrand, Gunn A., Scheffler, Katja, Suganthan, Rajikala, Rolseth, Veslemoy, Kusnierczyk, Anna, Rowe, Alexander D., Vagbo, Cathrine B., Vetlesen, Susanne, Eide, Lars, Slupphaug, Geir, Nakabeppu, Yusaku, Bredy, Timothy W., Klungland, Arne and Bjoras, Magnar (2015) Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice. Cell Reports, 13 12: 2671-2678. doi:10.1016/j.celrep.2015.12.001
Baker-Andresen, Danay, Zhao, Qiongyi, Li, Xiang, Jupp, Bianca, Chesworth, Rose, Lawrence, Andrew J. and Bredy, Timothy (2015) Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice. Neuroepigenetics, 4 1-11. doi:10.1016/j.nepig.2015.10.001
Spadaro, Paola A., Flavell, Charlotte R., Widagdo, Jocelyn, Ratnu, Vikram S., Troup, Michael, Ragan, Chikako, Mattick, John S. and Bredy, Timothy W. (2015) Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice. Biological Psychiatry, 78 12: 848-859. doi:10.1016/j.biopsych.2015.02.004
Ratnu, Vikram S., Wei, Wei and Bredy, Timothy W. (2014) Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons. European Journal of Neuroscience, 40 7: 3032-3039. doi:10.1111/ejn.12678
Li, X., Baker-Andresen, D., Zhao, Q., Marshall, V. and Bredy, T. W. (2014) Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation.Genes, Brain and Behavior, 13 7: 721-731. doi:10.1111/gbb.12150
Li, Xiang, Wei, Wei, Zhao, Qiong-Yi, Widagdo, Jocelyn, Baker-Andresen, Danay, Flavell, Charlotte R., D'Alessio, Ana, Zhang, Yi and Bredy, Timothy W. (2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proceedings of the National Academy of Sciences, 111 19: 7120-7125. doi:10.1073/pnas.1318906111
Fenton, Georgina E., Pollard, Amelia K, Halliday, David M., Mason, Rob, Bredy, Timothy W. and Stevenson, Carl W. (2014) Persistent prelimbic cortex activity contributes to enhanced learned fear expression in females. Learning and Memory, 21 2: 55-60. doi:10.1101/lm.033514.113
Flavell, Charlotte R., Lambert, Elliot A., Winters, Boyer D. and Bredy, Timothy W. (2013) Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction. Frontiers in Behavioral Neuroscience,7 DEC: 214.1-214.11. doi:10.3389/fnbeh.2013.00214
Ploense, Kyle L., Kerstetter, Kerry A., Wade, Matthew A., Woodward, Nicholas C., Maliniak, Dan, Reyes, Michael, Uchizono, Russell S., Bredy, Timothy W. and Kippin, Tod E. (2013) Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior. Behavioural Pharmacology, 24 3: 164-171. doi:10.1097/FBP.0b013e32836104ea
Baker-Andresen, Danay, Flavell, Charlotte R., Li, Xiang and Bredy, Timothy W. (2013) Activation of BDNF signaling prevents the return of fear in female mice. Learning & Memory, 20 5: 237-240. doi:10.1101/lm.029520.112
Marek, Roger, Strobel, Cornelia, Bredy, Timothy W. and Sah, Pankaj (2013) The amygdala and medial prefrontal cortex: partners in the fear circuit. Journal of Physiology, 591 10: 2381-2391. doi:10.1113/jphysiol.2012.248575
Baker-Andresen, Danay, Ratnu, Vikram and Bredy, Timothy (2013) Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Trends In Neurosciences, 36 1: 3-13. doi:10.1016/j.tins.2012.09.003
Li, Xiang, Wei, Wei, Ratnu, Vikram and Bredy, Timothy (2013) On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Neurobiology of Learning and Memory,105 125-132. doi:10.1016/j.nlm.2013.06.009
Barry, Guy, Briggs, J. A., Vanichkina, D. P., Poth, E. M., Beveridge, N. J., Vikram Ratnu, Nayler, S. P., Nones, K., Hu, J., Timothy Bredy, Nakagawa, S., Rigo, F., Taft, R. J., Cairns, M. J., Blackshaw, S., Wolvetang, E. J. and Mattick, J. S. (2013) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry, 19 4: 486-494. doi:10.1038/mp.2013.45
Wei, Wei, Coelho, Carlos M., Li, Xiang, Marek, Roger, Yan, Shanzhi, Anderson, Shawn, Meyers, David, Mukherjee, Chandrani, Sbardella, Gianluca, Castellano, Sabrina, Milite, Ciro, Rotili, Dante, Mai, Antonello, Cole, Philip A., Sah, Pankaj, Kobor, Michael S. and Bredy, Timothy W. (2012) p300/CBP-associated factor selectively regulates the extinction of conditioned fear. Journal of Neuroscience, 32 35: 11930-11941. doi:10.1523/JNEUROSCI.0178-12.2012
Spadaro, Paola A. and Bredy, Timothy W. (2012) Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders. Frontiers in Genetics, 3 JUL: 132.1-132.16. doi:10.3389/fgene.2012.00132
Lin, Quan, Wei, Wei, Coelho, Carlos M., Li, Xiang, Baker-Andresen, Dannay, Dudley, Kevin, Ratnu, Vikram S., Boskovic, Zoran, Kobor, Michael S., Sun, Yi E. and Bredy, Timothy W. (2011) The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory. Nature Neuroscience, 14 9: 1115-1117. doi:10.1038/nn.2891
Bredy, Timothy W., Lin, Quan, Wei, Wei, Baker-Andresen, Danay and Mattick, John S. (2011) MicroRNA regulation of neural plasticity and memory. Neurobiology of Learning and Memory, 96 1: 89-94. doi:10.1016/j.nlm.2011.04.004
Dudley, Kevin J., Li, Xiang, Kobor, Michael S., Kippin, Tod E. and Bredy, Timothy W. (2011) Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders. Neuroscience and Biobehavioral Reviews, 35 7: 1544-1551. doi:10.1016/j.neubiorev.2010.12.016
Marek, Roger, Coelho, Carlos M., Sullivan, Robert K. P., Baker-Andresen, Danay, Li, Xiang, Ratnu, Vikram, Dudley, Kevin J., Meyers, David, Mukherjee, Chandrani, Cole, Philip A., Sah, Pankaj and Bredy, Timothy W. (2011) Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. Journal of Neuroscience, 31 20: 7486-7491. doi:10.1523/JNEUROSCI.0133-11.2011
Bredy, Timothy W., Sun, Yi E. and Kobor, Michael S. (2010) How the epigenome contributes to the development of psychiatric disorders. Developmental Psychobiology, 52 4: 331-342. doi:10.1002/dev.20424
Helmekea, C., Seidel, K., Poeggel, G., Bredy, Timothy, Abraham, A. and Braun, K. (2009) Paternal deprivation during infancy results in dendrite- and time-specific changes of dendritic development and spine formation in the orbitofrontal cortex of the biparental rodent Octodon degus. Neuroscience, 163 3: 790-798. doi:10.1016/j.neuroscience.2009.07.008
Bredy, Timothy W. and Barad, Mark (2009) Social modulation of associative fear learning by pheromone communication. Learning and Memory, 16 1: 12-18. doi:10.1101/lm.1226009
Timothy, Bredy and Barad, Mark (2008) The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learning & Memory, 15 1: 39-45. doi:10.1101/lm.801108
Bredy, Timothy, Wu, Hao, Crego, Cortney, Zellhoefer, Jessica, Sun, Yi E. and Barad, Mark (2007) Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learning & Memory, 14 4: 268-276. doi:10.1101/lm.500907
Bredy, Timothy W., Brown, Richard E. and Meaney, Michael J. (2007) Effect of resource availability on biparental care, and offspring neural and behavioral development in the California mouse (Peromyscus californicus). European Journal of Neuroscience, 25 2: 567-575. doi:10.1111/j.1460-9568.2006.05266.x
Bredy, Timothy (2006) Behavioural epigenetics and psychiatric disorders. Medical Hypotheses, 68 2: 453-453. doi:10.1016/j.mehy.2006.07.009
Zhang, Tie-Yuan, Bagot, Rose, Parenta, Carine, Nesbitt, Cathy, Bredy, Timothy W., Caldji, Christian, Fish, Eric, Anisman, Hymie, Szyf, Moshe and Meaney, Michael J. (2006) Maternal programming of defensive responses through sustained effects on gene expression. Biological Psychology, 73 1: 72-89. doi:10.1016/j.biopsycho.2006.01.009
Epigenetic signatures of abnormal adult neurogenesis in Rett syndrome
(2017–2019) NHMRC Project Grant
Exercise reverses cognitive decline in aged animals by growth hormone stimulation of neurogenesis in the hippocampus
(2017–2019) NHMRC Project Grant
Stafford Fox Program in prevention of ageing and dementia
(2016–2019) The Stafford Fox Medical Research Foundation
Light-sheet microscope for high-speed 3D imaging of live organisms and fixed tissue
(2016) NHMRC Equipment Grant
Single Cell Transcriptomic Laboratory
(2016) UQ Major Equipment and Infrastructure
- Professor Rongqiao He, QBI-IBP Joint Laboratory of Neuroscience and Cognition, with the Institute of Biophysics, Beijing, China.
- Professor Huji Xu, Joint Sino-Australian Neurogenetics Laboratory with the Second Military Medical University (SMMU), Shanghai, China.
- Matt Brown, The University of Queensland
- Peter Visscher, The University of Queensland
- Bryan Mowry, QBI, The University of Queensland
- David Reutens, The University of Queensland
- Dr Vidita Vaidya, Tata Institute of Fundamental Research, Mumbai, India
- Professor Dongyuan Zhao, Fudan University, Shanghai, China
- Max Lu, University of Surrey, England
- Gordon Xu, The University of Queensland
- Helen Cooper, QBI, The University of Queensland
- Professors Trevor Kilpatrick and Seong-Seng Tan, University of Melbourne.
- Pankaj Sah, QBI, The University of Queensland
- Professor Andrew Boyd, Queensland Institute of Medical Research.
Optimising exercise for cognitive function in older adults
It is well known that exercise has a positive influence on cognitive function during aging. However, the optimal dose, intensity and duration of exercise for improving cognitive function is not known, nor are the mechanisms by which exercise may prevent or even reverse cognitive decline.
Join our study to help identify the ‘sweet spot’ for exercise and memory. How much is enough? How much is too little?
Are you aged 65 – 85 and do you want to:
- become more physically active?
- participate in regular supervised exercise?
- learn more about you brain health, learning and memory?
- be part of supportive community?
Healthy men and women aged 65–85 are invited to participate in a six-month supervised exercise program. To be eligible participants must have no history of stroke or brain trauma, no diagnosed mental illness or cognitive function impairment, be free of significant cardiovascular disease, have a healthy BMI (< 30 kg/m2) and be able and willing to commit to the duration of the exercise program. Participation will include fitness tests, cognitive function testing, MRI scans of the brain, and small blood samples.
Participants will be divided into three groups to complete either low-intensity (very easy), moderate-intensity (easy) exercise or aerobic-interval (hard) exercise three times per week for six months. All exercise will be supervised and monitored and we will measure cognitive function, fitness, blood hormones, genetic factors and brain volume before beginning exercise, at regular interval during the exercise program and six months following the conclusion of the exercise program.
Contact Dr Mia Schaumberg and the Healthy Brain-Ageing Team (email@example.com) for further details.
The Healthy Brain-Ageing Team
The Stafford Fox Exercise and Healthy Brain-Ageing Centre
School of Human Movement and Nutrition Sciences (Building 26B)
The University of Queensland | St Lucia, QLD, 4072 | Australia
+61 7 3346 8770