Professor Tim Karl

Professor Tim Karl

Professor, Behavioural Neuroscience,
School of Medicine

Professor, Behavioural Neuroscience,
School of Medicine

Biography

Tim Karl graduated from the Leipniz University of Hanover (Germany) in 2003 with a PhD in Zoology (Behavioural Neuroscience). Until 2008, he was a postdoctoral researcher at the Garvan Institute working on rodent models for anxiety and schizophrenia. In 2008, Tim Karl established his own research team at Neuroscience Research Australia (NeuRA). His research focused on the neuro-behavioural consequences of gene-environment interactions in animal models for schizophrenia and the discovery of new therapeutic targets for Alzheimer's disease. In 2016, Tim Karl moved to Western Sydney University, where he continues his preclinical research into schizophrenia and Alzheimer's disease. He also investigates the detrimental and potentially beneficial properties of cannabis constituents for brain disorders. Finally, Tim's research aims to enhance the validity of rodent models and the well-being of test animals in medical research by providing more stimulating housing conditions and utilising more natural test system models.

Prof Karl is currently funded by the National Health and Medical Research Council (NHMRC Project Grants, Dementia Research Team Initiative) and the Rebecca L Cooper Medical Research Foundation and has received funding from NHMRC, the Motor Neuron Disease Research Institute of Australia, the Brain and Behavior Research Foundation (USA), the German Research Foundation (DFG), and other funding bodies (e.g. Mason Foundation National Research Program, Ramaciotti Foundation) in the past.

Prof Karl is the Chair of the Animal Care and Ethics Committee at Western Sydney University.

For more details on research, facilities and funding, please go to https://www.westernsydney.edu.au/medicine/som/research/behavioural_neuroscience.

This information has been contributed by Professor Karl.

Qualifications

  • DNatSc Leibniz University of Hanover

Professional Memberships

  • Biological Psychiaty Australia (2014)
  • International Behavioral Neuroscience Society (2013)
  • Australasian Neuroscience Society (2008)

Interests

  • Behavioural Neuroscience
  • Gene-environment interactions
  • Mouse models
  • Pharmacology
  • Preclinical research into brain disorders
  • Schizophrenia

Organisational Unit (School / Division)

  • School of Medicine
  • School of Medicine

Committees

  • Animal Care and Ethics Committee, WSU
  • Admissions Committee, School of Medicine
  • Institutional Biosafey Committee, ANSTO
  • Scientific Advisory Committee, Rebecca L. Cooper Medical Research Foundation
  • School Research and Higher Degree Committee, School of Medicine

Contact

Email: T.Karl@westernsydney.edu.au
Phone: (02) 4620 3040
Mobile: 0400420271
Location: 30.2.19
Campbelltown

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Teaching

Previous Teaching Areas

  • 300892 Medical Science Project, 2017
  • 300892 Medical Science Project, 2018
  • 300937 Advanced Science Project A, 2017
  • 300937 Advanced Science Project A, 2018
  • 400862 Foundations of Medicine 2, 2017
  • 400862 Foundations of Medicine 2, 2018
  • 800192 Neuroscience Methods, 2018

Publications

Chapters in Books

  • Chesworth, R., Watt, G. and Karl, T. (2018), 'Cannabinoid modulation of object recognition and location memory : a preclinical assessment', Handbook of Object Novelty Recognition. Volume 27, Elsevier 9780128120125.
  • Karl, T. and Arnold, J. (2017), 'The interactive nature of cannabis and schizophrenia risk genes', Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis and Treatment, Academic Press 9780128007563.
  • Ellenbroek, B. and Karl, T. (2016), 'Genetic rat models for schizophrenia', Modeling the Psychopathological Dimensions of Schizophrenia: From Molecules to Behavior, Academic Press 9780128009819.
  • Karl, T. and Arnold, J. (2014), 'Cannabis abuse and dependence', Behavioral Genetics of the Mouse. Vol. 2, Genetic Mouse Models of Neurobehavioural Disorders, Cambridge University Press 9781107044456.
  • Karl, T. and Arnold, J. (2014), 'What does a mouse tell us about neuregulin 1-cannabis interactions?', Mapping the Pathophysiology of Schizophrenia: Interactions Between Multiple Cellular Pathways, Frontiers Media 9782889191994.
  • Horsten, S., Hoffmann, T., Alfalah, M., Wrann, C., Karl, T., Pabst, R. and Bedoui, S. (2004), 'PP, PYY and NPY : synthesis, storage, release and degradation', Neuropeptide Y and Related Peptides, Springer 9783540405818.

Journal Articles

  • Zieba, J., Morris, M., Weickert, C. and Karl, T. (2020), 'Behavioural effects of high fat diet in adult Nrg1 type III transgenic mice', Behavioural Brain Research, vol 377 .
  • Watt, G., Przybyla, M., Zak, V., Eersel, J., Ittner, A., Ittner, L. and Karl, T. (2020), 'Novel behavioural characteristics of male human P301S mutant tau transgenic mice : a model for tauopathy', Neuroscience, vol 431 , pp 166 - 175.
  • Przybyla, M., Eersel, J., Hummel, A., Hoven, J., Sabale, M., Harasta, A., Muller, J., Gajwani, M., Prikas, E., Mueller, T., Stevens, C., Power, J., Housley, G., Karl, T., Kassiou, M., Ke, Y., Ittner, A. and Ittner, L. (2020), '[In Press] Onset of hippocampal network aberration and memory deficits in P301S tau mice are associated with an early gene signature', Brain, .
  • Clarke, D., Chohan, T., Kassem, M., Smith, K., Chesworth, R., Karl, T., Kuligowski, M., Fok, S., Bennett, M. and Arnold, J. (2019), 'Neuregulin 1 deficiency modulates adolescent stress-induced dendritic spine loss in a brain region-specific manner and increases complement 4 expression in the hippocampus', Schizophrenia Bulletin, vol 45, no 2 , pp 339 - 349.
  • Mirzaei, M., Pushpitha, K., Deng, L., Chitranshi, N., Gupta, V., Rajput, R., Mangani, A., Dheer, Y., Godinez, A., McKay, M., Kamath, K., Pascovici, D., Wu, J., Salekdeh, G., Karl, T., Haynes, P., Graham, S. and Gupta, V. (2019), 'Upregulation of proteolytic pathways and altered protein biosynthesis underlie retinal pathology in a mouse model of Alzheimer's disease', Molecular Neurobiology, vol 56, no 9 , pp 6017 - 6034.
  • Gyengesi, E., Rangel, A., Ullah, F., Liang, H., Niedermayer, G., Asgarov, R., Venigalla, M., Gunawardena, D., Karl, T. and Muench, G. (2019), 'Chronic microglial activation in the GFAP-IL6 mouse contributes to age-dependent cerebellar volume loss and impairment in motor function', Frontiers in Neuroscience, vol 13 .
  • Zieba, J., Uddin, G., Youngson, N., Karl, T. and Morris, M. (2019), 'Long-term behavioural effects of maternal obesity in C57BL/6J mice', Physiology and Behavior, vol 199 , pp 306 - 313.
  • Sharman, M., Gyengesi, E., Liang, H., Chatterjee, P., Karl, T., Li, Q., Wenk, M., Halliwell, B., Martins, R. and Muench, G. (2019), 'Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and a-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease : are combinations more effective?', Neurobiology of Disease, vol 124 , pp 505 - 519.
  • Zieba, J., Sinclair, D., Sebree, T., Bonn-Miller, M., Gutterman, D., Siegel, S. and Karl, T. (2019), 'Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP-independent mechanism', Pharmacology Biochemistry and Behavior, vol 181 , pp 93 - 100.
  • Sharman, M., Verdile, G., Shanmugam, K., Parenti, C., Singh, A., Watt, G., Karl, T., Chang, D., Li, C. and Muench, G. (2019), 'Targeting inflammatory pathways in Alzheimer's disease : a focus on natural products and phytomedicines', CNS Drugs, vol 33, no 5 , pp 457 - 480.
  • Zieba, J., Morris, M. and Karl, T. (2019), 'Behavioural effects of high fat diet exposure starting in late adolescence in neuregulin 1 transmembrane domain mutant mice', Behavioural Brain Research, vol 373 .
  • Kreilaus, F., Chesworth, R., Eapen, V., Clarke, R. and Karl, T. (2019), 'First behavioural assessment of a novel Immp2l knockdown mouse model with relevance for Gilles de la Tourette syndrome and Autism spectrum disorder', Behavioural Brain Research, vol 374 .
  • Kreilaus, F., Guerra, S., Masanetz, R., Menne, V., Yerbury, J. and Karl, T. (2019), '[In Press] Novel behavioural characteristics of the superoxide dismutase 1 G93A (SOD1G93A) mouse model of amyotrophic lateral sclerosis include sex-dependent phenotypes', Genes, Brain and Behavior, .
  • Lei, M., Teo, J., Song, H., McEwen, H., Lee, J., Couttas, T., Duncan, T., Chesworth, R., Bertz, J., Przybyla, M., Eersel, J., Heng, B., Guillemin, G., Ittner, L., Fath, T., Garner, B., Ittner, A., Karl, T. and Don, A. (2019), 'Sphingosine kinase 2 potentiates amyloid deposition but protects against hippocampal volume loss and demyelination in a mouse model of Alzheimer's disease', The Journal of Neuroscience, vol 39, no 48 , pp 9645 - 9659.
  • Chesworth, R., Long, L., Weickert, C. and Karl, T. (2018), 'The endocannabinoid system across postnatal development in transmembrane domain neuregulin 1 mutant mice', Frontiers in Psychiatry, vol 9 .
  • Olaya, J., Heusner, C., Matsumoto, M., Sinclair, D., Kondo, M., Karl, T. and Weickert, C. (2018), 'Overexpression of Neuregulin-1 type III confers hippocampal mRNA alterations and schizophrenia-like behaviours in mice', Schizophrenia Bulletin, vol 44, no 4 , pp 865 - 875.
  • Kim, W., Fu, Y., Dobson-Stone, C., Hsiao, J., Shang, K., Hallupp, M., Schofield, P., Garner, B., Karl, T. and Kwok, J. (2018), 'Effect of fluvoxamine on amyloid-? peptide generation and memory', Journal of Alzheimer's Disease, vol 62, no 4 , pp 1777 - 1787.
  • Olaya, J., Heusner, C., Matsumoto, M., Weickert, C. and Karl, T. (2018), 'Schizophrenia-relevant behaviours of female mice overexpressing neuregulin 1 type III', Behavioural Brain Research, vol 353 , pp 227 - 235.
  • Lloyd, D., Talmage, D., Weickert, C. and Karl, T. (2018), 'Reduced type III neuregulin 1 expression does not modulate the behavioural sensitivity of mice to acute Delta 9-tetrahydrocannabinol (D9-THC)', Pharmacology, Biochemistry and Behavior, vol 170 , pp 64 - 70.
  • Zhang, L., Ip, C., Lee, I., Qi, Y., Reed, F., Karl, T., Low, J., Enriquez, R., Lee, N., Baldock, P. and Herzog, H. (2018), 'Diet-induced adaptive thermogenesis requires neuropeptide FF receptor-2 signalling', Nature Communications, vol 9 .
  • Low, J., Ambikairajah, A., Shang, K., Brown, D., Tsai, V., Breit, S. and Karl, T. (2017), 'First behavioural characterisation of a knockout mouse model for the transforming growth factor (TGF)-? superfamily cytokine, MIC-1/GDF15', PLoS One, vol 12, no 1 .
  • Watt, G. and Karl, T. (2017), 'In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer's disease', Frontiers in Pharmacology, vol 8 .
  • Karl, T., Garner, B. and Cheng, D. (2017), 'The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer's disease', Behavioural Pharmacology, vol 28, no 2-3 , pp 142 - 160.
  • Lei, M., Shafique, A., Shang, K., Couttas, T., Zhao, H., Don, A. and Karl, T. (2017), 'Contextual fear conditioning is enhanced in mice lacking functional sphingosine kinase 2', Brain Research Bulletin, vol 333 , pp 9 - 16.
  • Shang, K., Talmage, D. and Karl, T. (2017), 'Parent-of-origin effects on schizophrenia-relevant behaviours of type III neuregulin 1 mutant mice', Behavioural Brain Research, vol 332 , pp 250 - 258.
  • Chesworth, R. and Karl, T. (2017), 'Molecular basis of cannabis-induced schizophrenia-relevant behaviours : insights from animal models', Current Behavioral Neuroscience Reports, vol 4, no 3 , pp 254 - 279.
  • Li, H., Ruberu, K., Karl, T. and Garner, B. (2016), 'Cerebral apolipoprotein-D Is hypoglycosylated compared to peripheral tissues and is variably expressed in mouse and human brain regions', PLoS One, vol 11, no 2 .
  • Holm-Hansen, S., Low, J., Zieba, J., Gjedde, A., Bergersen, L. and Karl, T. (2016), 'Behavioural effects of high fat diet in a mutant mouse model for the schizophrenia risk gene neuregulin 1', Genes, Brain and Behavior, vol 15, no 3 , pp 295 - 304.
  • Li, H., Karl, T. and Garner, B. (2016), 'Abca7 deletion does not affect adult neurogenesis in the mouse', Bioscience Reports, vol 36, no 2 .
  • Mostaid, M., Lloyd, D., Liberg, B., Sundram, S., Pereira, A., Pantelis, C., Karl, T., Weickert, C., Everall, I. and Bousman, C. (2016), 'Neuregulin-1 and schizophrenia in the genome-wide association study era', Neurosciene and Biobehavioral Reviews, vol 68 , pp 387 - 409.
  • Przybyla, M., Stevens, C., Hoven, J., Harasta, A., Bi, M., Ittner, A., Hummel, A., Hodges, J., Piguet, O., Karl, T., Kassiou, M., Housley, G., Ke, Y., Ittner, L. and Eersel, J. (2016), 'Disinhibition-like behavior in a P301S mutant tau transgenic mouse model of frontotemporal dementia', Neuroscience Letters, vol 631 , pp 24 - 29.
  • Li, H., Ruberu, K., Munoz, S., Jenner, A., Spiro, A., Zhao, H., Rassart, E., Sanchez, D., Ganfornina, M., Karl, T. and Garner, B. (2015), 'Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice', Neurobiology of Aging, vol 36, no 5 , pp 1820 - 1833.
  • Long, L., Anderson, P., Frank, E., Shaw, A., Liu, S., Huang, X., Pinault, D., Karl, T., O'Brien, T., Weickert, C. and Jones, N. (2015), 'Neuregulin 1 expression and electrophysiological abnormalities in the Neuregulin 1 transmembrane domain heterozygous mutant mouse', PLoS One, vol 10, no 5 .
  • Zieba, J., Low, J., Purtell, L., Qi, Y., Campbell, L., Herzog, H. and Karl, T. (2015), 'Behavioural characteristics of the Prader-Willi syndrome related biallelic Snord116 mouse model', Neuropeptides, vol 53 , pp 71 - 77.
  • Purves-Tyson, T., Boerrigter, D., Allen, K., Zavitsanou, K., Karl, T., Djunaidi, V., Double, K., Desai, R., Handelsman, D. and Weickert, C. (2015), 'Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats', Hormones and Behavior, vol 70 , pp 73 - 84.
  • Engel, M., Snikeris, P., Jenner, A., Karl, T., Huang, X. and Frank, E. (2015), 'Neuregulin 1 prevents phencyclidine-induced behavioral impairments and disruptions to GABAergic signaling in mice', International Journal of Neuropsychopharmacology, vol 18, no 7 , pp 1 - 11.
  • Harasta, A., Power, J., Jonquieres, G., Karl, T., Drucker, D., Housley, G., Schneider, M. and Klugmann, M. (2015), 'Septal glucagon-like peptide 1 receptor expression determines suppression of cocaine-induced behavior', Neuropsychopharmacology, vol 40, no 8 , pp 1969 - 1978.
  • Li, H., Karl, T. and Garner, B. (2015), 'Understanding the function of ABCA7 in Alzheimer's disease', Biochemical Society Transactions, vol 43, no 5 , pp 920 - 923.
  • Cheng, D., Spiro, A., Jenner, A., Garner, B. and Karl, T. (2014), 'Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice', Journal of Alzheimer's Disease, vol 42, no 4 , pp 1383 - 1396.
  • Baldock, P., Lin, S., Zhang, L., Karl, T., Shi, Y., Driessler, F., Zengin, A., Hormer, B., Lee, N. and et al, .. (2014), 'Neuropeptide Y attenuates stress-induced bone loss through suppression of noradrenaline circuits', Journal of Bone and Mineral Research, vol 29, no 10 , pp 2238 - 2249.
  • Chohan, T., Boucher, A., Spencer, J., Kassem, M., Hamdi, A., Karl, T., Fok, S., Bennett, M. and Arnold, J. (2014), 'Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice', Schizophrenia Bulletin, vol 40, no 6 , pp 1272 - 1284.
  • Logge, W., Kingham, J. and Karl, T. (2014), 'Do individually ventilated cage systems generate a problem for genetic mouse model research?', Genes, Brain and Behavior, vol 13, no 7 , pp 713 - 720.
  • Cheng, D., Low, J., Logge, W., Garner, B. and Karl, T. (2014), 'Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1^E9 mice', Psychopharmacology, vol 231, no 15 , pp 3009 - 3017.
  • Cheng, D., Low, J., Logge, W., Garner, B. and Karl, T. (2014), 'Novel behavioural characteristics of female APPSwe/PS1oE9 double transgenic mice', Behavioural Brain Research, vol 260 , pp 111 - 118.
  • Zavitsanou, K., Lim, C., Purves-Tyson, T., Karl, T., Kassiou, M., Banister, S., Guillemin, G. and Weickert, C. (2014), 'Effect of maternal immune activation on the kynurenine pathway in preadolescent rat offspring and on MK801-induced hyperlocomotion in adulthood : amelioration by COX-2 inhibition', Brain, Behavior, and Immunity, vol 41, no 1 , pp 173 - 181.
  • Karl, T. and Arnold, J. (2014), 'Schizophrenia : a consequence of gene-environment interactions?', Frontiers in Behavioral Neuroscience, vol 8 .
  • Logge, W., Kingham, J. and Karl, T. (2013), 'Behavioural consequences of IVC cages on male and female C57BL/6J mice', Neuroscience, vol 237 , pp 285 - 293.
  • Newell, K., Karl, T. and Huang, X. (2013), 'A neuregulin 1 transmembrane domain mutation causes imbalanced glutamatergic and dopaminergic receptor expression in mice', Neuroscience, vol 248 , pp 670 - 680.
  • Kim, W., Li, H., Ruberu, K., Chan, S., Elliott, D., Low, J., Cheng, D., Karl, T. and Garner, B. (2013), 'Deletion of Abca7 increases cerebral amyloid-? accumulation in the J20 mouse model of Alzheimer's disease', Journal of Neuroscience, vol 33, no 10 , pp 4387 - 4394.
  • Cheng, D., Logge, W., Low, J., Garner, B. and Karl, T. (2013), 'Novel behavioural characteristics of the APPSwe/PS1^E9 transgenic mouse model of Alzheimer's disease', Behavioural Brain Research, vol 245 , pp 120 - 127.
  • Spencer, J., Darbyshire, K., Boucher, A., Kashem, M., Long, L., McGregor, I., Karl, T. and Arnold, J. (2013), 'Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence : a hippocampal proteomic study in mice', Frontiers in Cellular Neuroscience, vol 7 .
  • Long, L., Chesworth, R., Huang, X., McGregor, I., Arnold, J. and Karl, T. (2013), 'Transmembrane domain Nrg1 mutant mice show altered susceptibility to the neurobehavioural actions of repeated THC exposure in adolescence', International Journal of Neuropsychopharmacology, vol 16, no 1 , pp 163 - 175.
  • Spencer, J., Chohan, T., Karl, T. and Arnold, J. (2013), 'Female neuregulin 1 heterozygous mice require repeated exposure to ^9-tetrahydrocannabinol to alter sensorimotor gating function', Pharmacopsychiatry, vol 46, no 7 , pp 286 - 291.
  • Karl, T. and Arnold, J. (2013), 'What does a mouse tell us about neuregulin 1 : cannabis interactions?', Frontiers in Cellular Neuroscience, vol 7 .
  • Karl, T. (2013), 'Neuregulin 1 : a prime candidate for research into gene-environment interactions in schizophrenia? : insights from genetic rodent models', Frontiers in Behavioral Neuroscience, vol 7 .
  • Karl, T., Cheng, D., Garner, B. and Arnold, J. (2012), 'The therapeutic potential of the endocannabinoid system for Alzheimer's disease', Expert Opinion on Therapeutic Targets, vol 16, no 4 , pp 407 - 420.
  • Chesworth, R., Yulyaningsih, E., Cappas, E., Arnold, J., Sainsbury, A. and Karl, T. (2012), 'The response of neuregulin 1 mutant mice to acute restraint stress', Neuroscience Letters, vol 515, no 1 , pp 82 - 86.
  • Long, L., Chesworth, R., Huang, X., Wong, A., Spiro, A., McGregor, I., Arnold, J. and Karl, T. (2012), 'Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice', PLoS ONE, vol 7, no 4 .
  • Karl, T., Bhatia, S., Cheng, D., Kim, W. and Garner, B. (2012), 'Cognitive phenotyping of amyloid precursor protein transgenic J20 mice', Behavioural Brain Research, vol 228, no 2 , pp 392 - 397.
  • Chesworth, R., Downey, L., Logge, W., Killcross, S. and Karl, T. (2012), 'Cognition in female transmembrane domain neuregulin 1 mutant mice', Behavioural Brain Research, vol 226, no 1 , pp 218 - 223.
  • Logge, W., Cheng, D., Chesworth, R., Bhatia, S., Garner, B., Kim, W. and Karl, T. (2012), 'Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases', PLoS One, vol 7, no 9 .
  • Arnold, J., Boucher, A. and Karl, T. (2012), 'The yin and yang of cannabis-induced psychosis : the actions of ^(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia', Current Pharmaceutical Design, vol 18, no 32 , pp 5113 - 5130.
  • Klein, C., Karanges, E., Spiro, A., Wong, A., Spencer, J., Huynh, T., Gunasekaran, N., Karl, T., Long, L., Huang, X., Liu, K., Arnold, J. and McGregor, I. (2011), 'Cannabidiol potentiates ^ 9-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats', Psychopharmacology, vol 218, no 2 , pp 443 - 457.
  • Karl, T., Burne, T., Buuse, M. and Chesworth, R. (2011), 'Do transmembrane domain neuregulin 1 mutant mice exhibit a reliable sensorimotor gating deficit?', Behavioural Brain Research, vol 223, no 2 , pp 336 - 341.
  • Boucher, A., Hunt, G., Micheau, J., Huang, X., McGregor, I., Karl, T. and Arnold, J. (2011), 'The schizophrenia susceptibility gene neuregulin 1 modulates tolerance to the effects of cannabinoids', International Journal of Neuropsychopharmacology, vol 14, no 5 , pp 631 - 643.
  • Duffy, L., Cappas, E., Lai, D., Boucher, A. and Karl, T. (2010), 'Cognition in transmembrane domain neuregulin 1 mutant mice', Neuroscience, vol 170, no 3 , pp 800 - 807.
  • Long, L., Chesworth, R., Huang, X., McGregor, I., Arnold, J. and Karl, T. (2010), 'A behavioural comparison of acute and chronic 9- tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice', International Journal of Neuropsychopharmacology, vol 13, no 7 , pp 861 - 876.
  • Karl, T., Chesworth, R., Duffy, L. and Herzog, H. (2010), 'Acoustic startle response and sensorimotor gating in a genetic mouse model for the Y1 receptor', Neuropeptides, vol 44, no 3 , pp 233 - 239.
  • Boy, J., Schmidt, T., Schumann, U., Grasshoff, U., Unser, S., Holzmann, C., Schmitt, I., Karl, T., Laccone, F., Wolburg, H., Ibrahim, S. and Riess, O. (2010), 'A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats', Neurobiology of Disease, vol 37, no 2 , pp 284 - 293.
  • Long, L., Chesworth, R., Arnold, J. and Karl, T. (2010), 'A follow-up study : acute behavioural effects of ^9-THC in female heterozygous Neuregulin 1 transmembrane domain mutant mice', Psychopharmacology, vol 211, no 3 , pp 277 - 289.
  • Karl, T., Chesworth, R., Duffy, L. and Herzog, H. (2010), 'Schizophrenia-relevant behaviours in a genetic mouse model for Y2 deficiency', Behavioural Brain Research, vol 207, no 2 , pp 434 - 440.
  • Lautenbach, A., Budde, A., Wrann, C., Teichmann, B., Vieten, G., Karl, T. and Nave, H. (2009), 'Obesity and the associated mediators leptin, estrogen and IGF-I enhance the cell proliferation and early tumorigenesis of breast cancer cells', Nutrition and Cancer, vol 61, no 4 , pp 484 - 491.
  • Buuse, M., Wischhof, L., Lee, R., Martin, S. and Karl, T. (2009), 'Neuregulin 1 hypomorphic mutant mice : enhanced baseline locomotor activity but normal psychotropic drug-induced hyperlocomotion and prepulse inhibition regulation', International Journal of Neuropsychopharmacology, vol 12, no 10 , pp 1383 - 1393.
  • Duffy, L., Cappas, E., Scimone, A., Schofield, P. and Karl, T. (2008), 'Behavioural profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1', Behavioral Neuroscience, vol 122, no 4 , pp 748 - 759.
  • Dean, B., Karl, T., Pavey, G., Boer, S., Duffy, L. and Scarr, E. (2008), 'Increased levels of cortical serotonin 2A receptors and serotonin transporter in the CNS of neuregulin 1 hypomorphic/mutant mice', Schizophrenia Research, vol 99, no 1 , pp 341 - 349.
  • Doyle, K., Karl, T., Hort, Y., Duffy, L., Shine, J. and Herzog, H. (2008), 'Y1 receptors are critical for the proliferation of adult mouse precursor cells in the olfactory neuroepithelium', Journal of Neurochemistry, vol 105, no 3 , pp 641 - 652.
  • Karl, T., Duffy, L. and Herzog, H. (2008), 'Behavioural profile of a new mouse model for NPY deficiency', European Journal of Neuroscience, vol 28, no 1 , pp 173 - 180.
  • Boucher, A., Arnold, J., Duffy, L., Schofield, P., Micheau, J. and Karl, T. (2007), 'Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of ^9-tetrahydrocannabinol', Psychopharmacology, vol 192, no 3 , pp 325 - 336.
  • Sainsbury, A., Lin, S., McNamara, K., Slack, K., Enriquez, R., Lee, N., Boey, D., Smythe, G., Schwarzer, C., Baldock, P., Karl, T., Lin, E., Michelle, C. and Herzog, H. (2007), 'Dynorphin knockout reduces fat mass and increases weight loss during fasting in mice', Molecular Endocrinology, vol 21, no 7 , pp 1722 - 1735.
  • Karl, T. and Herzog, H. (2007), 'Behavioral profiling of NPY in aggression and neuropsychiatric diseases', Peptides, vol 28, no 2 , pp 326 - 333.
  • Karl, T., Duffy, L., Scimone, A., Harvey, R. and Schofield, P. (2007), 'Altered motor activity, exploration, and anxiety in heterozygous neuregulin 1 mutant mice : implications for understanding schizophrenia', Genes, Brain and Behavior, vol 6, no 7 , pp 677 - 687.
  • Boucher, A., Hunt, G., Karl, T., Micheau, J., McGregor, I. and Arnold, J. (2007), 'Heterozygous neuregulin 1 mice display greater baseline and ^9-tetrahydocannabinol-induced c-Fos expression', Neuroscience, vol 149, no 4 , pp 861 - 870.
  • Frerker, N., Wagner, L., Wolf, R., Heiser, U., Hoffmann, T., Rahfeld, J., Schade, J., Karl, T., Naim, H., Alfalah, M., Demuth, H. and Horsten, S. (2007), 'Neuropeptide Y (NPY) cleaving enzymes : structural and functional homologs of dipeptidyl peptidase 4', Peptides, vol 28, no 2 , pp 257 - 268.
  • Karl, T., Duffy, L., O'Brien, E., Matsumoto, I. and Dedova, I. (2006), 'Behavioural effects of chronic haloperidol and risperidone treatment in rats', Behavioural Brain Research, vol 171, no 2 , pp 286 - 294.
  • O'Brien, E., Dedova, I., Duffy, L., Cordwell, S., Karl, T. and Matsumoto, I. (2006), 'Effects of chronic risperidone treatment on the striatal protein profiles in rats', Brain Research, vol 1113, no 1 , pp 24 - 32.
  • Lin, E., Lee, N., Slack, K., Karl, T., Duffy, L., Matsumoto, I., Dedova, I., Herzog, H. and Sainsbury, A. (2006), 'Distinct endocrine effects of chronic haloperidol or risperidone administration to male rats', Neuropharmacology, vol 51, no 7-8 , pp 1129 - 1136.
  • Karl, T., Burne, T. and Herzog, H. (2006), 'Effect of Y1 receptor deficiency on motor activity, exploration, and anxiety', Behavioural Brain Research, vol 167, no 1 , pp 87 - 93.
  • Dallmann, R., Steinlechner, S., Horsten, S. and Karl, T. (2006), 'Stress-induced hyperthermia in the rat : comparison of classical and novel recording methods', Laboratory Animals, vol 40, no 2 , pp 186 - 193.
  • Sainsbury, A., Bergen, H., Boey, D., Bamming, D., Cooney, G., Lin, S., Couzens, M., Stroth, N., Lee, N., Lindner, D., Singewald, N., Karl, T., Duffy, L., Enriquez, R., Slack, K., Sperk, G. and Herzog, H. (2006), 'Y2Y4 receptor double knockout protects against obesity due to a high-fat diet or Y1 receptor deficiency in mice', Diabetes, vol 55, no 1 , pp 19 - 26.
  • Boey, D., Lin, S., Karl, T., Baldock, P., Lee, N., Enriquez, R., Couzens, M., Slack, K., Dallmann, R., Sainsbury, A. and Herzog, H. (2006), 'Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity', Diabetologia, vol 49, no 6 , pp 1360 - 1370.
  • Karl, T., Lin, S., Schwarzer, C., Sainsbury, A., Couzens, M., Wittmann, W., Boey, D., Horsten, S. and Herzog, H. (2004), 'Y1 receptors regulate aggressive behavior by modulating serotonin pathways', Proceedings of the National Academy of Sciences of the United States of America, vol 101, no 34 , pp 12742 - 12747.
  • Karl, T., Chwalisz, W., Wedekind, D., Hedrich, H., Hoffmann, T., Jacobs, R., Pabst, R. and Horsten, S. (2003), 'Localization, transmission, spontaneous mutations, and variation of function of the Dpp4 (Dipeptidyl-peptidase IV; CD26) gene in rats', Regulatory Peptides, vol 115, no 2 , pp 81 - 90.
  • Karl, T., Hoffmann, T., Pabst, R. and Horsten, S. (2003), 'Behavioral effects of neuropeptide Y in F344 rat substrains with a reduced dipeptidyl-peptidase IV activity', Pharmacology, Biochemistry and Behavior, vol 75, no 4 , pp 869 - 879.
  • Karl, T., Pabst, R. and Horsten, S. (2003), 'Behavioral phenotyping of mice in pharmacological and toxicological research', Experimental and Toxicologic Pathology, vol 55, no 1 , pp 69 - 83.
  • Karl, T., Hoffmann, T., Pabst, R. and Horsten, S. (2003), 'Extreme reduction of dipeptidyl peptidase IV activity in F344 rat substrains is associated with various behavioral differences', Physiology and Behavior, vol 80, no 1 , pp 123 - 134.

Conference Papers

  • Liang, H., Sonego, S., Gyengesi, E., Rangel, A., Niedermayer, G., Karl, T. and Muench, G. (2017), 'Anti-inflammatory and neuroprotective effect of apigenin : studies in the GFAP-IL6 mouse model of chronic neuroinflammation', Oxygen Club of California. World Congress, Berlin, Germany.

Genetic mouse models for schizophrenia: the candidate gene neuregulin 1

Schizophrenia is a chronic and disabling mental disorder that affects 1% of the world’s population. Neither environment nor genetics alone are sufficient to cause schizophrenia. Rodent models for schizophrenia risk genes (e.g. neuregulin 1) are capable of partially modelling disease aetiology (i.e. endophenotypes) and clarifying the impact of these genes on behaviour and brain development. However, to model this mental disorder in its full complexity, it is important to develop multi-factorial animal models combining genetic and environmental risk factors (e.g. chronic cannabis abuse, unhealthy diet, early life stress) for schizophrenia. My team focuses on the neuro-behavioural characterisation of these models, applying a multitude of different behavioural phenotyping paradigms.

The role of the endocannabinoid system in Alzheimer’s disease

Alzheimer’s disease is neurodegenerative cognitive disorder with an inflammatory component. More classically, Alzheimer's disease is described by extracellular amyloid deposition (building senile plaques) and tau hyper-phosphorylation (forming intracellular neurofibrillary tangles). These processes also impact on a variety of neurotransmitter systems and increased lipid peroxidation is found in affected brains supporting a role for oxidative damage in this disorder as well. Interestingly, the endocannabinoid system (eCB) plays a role in immunity, neuroprotection (i.e. anti-inflammatory and anti-oxidative effects) and can affect cognitive domains. Recent animal research suggests that manipulations to the eCB might have beneficial effects on the pathophysiology of Alzheimer's disease and disease-related cognitive impairments. Thus, my team evaluates the neuro-behavioural response of genetic mouse models for Alzheimer's disease to cannabinoid challenge with a particular focus on the effects of the non-psychoactive phytocannabinoid cannabidiol (CBD).

Housing conditions affect rodent model research

Behavioural, cellular and molecular studies have revealed a significant beneficial impact of environmental enrichment (EE; housing conditions that facilitate enhanced sensory, cognitive and motor stimulation) on brain development and behaviour. Enrichment can minimise adverse neurobehavioural effects of age, pharmacological/genetic manipulation and early life intervention in laboratory rodent models. Furthermore, enrichment has the potential to increase animal welfare for laboratory animals. However, enrichment protocols vary widely across laboratories, as does the degree to which enrichment is part of so-called standard laboratory housing conditions. As enrichment can modulate or even rescue the phenotype of animal models, my team is interested in systematically evaluating the effects of enrichment on rodent models in more detail, using neuro-behavioural phenotyping techniques. We also investigate how a new form of rodent housing (i.e. individually ventilated rack systems: IVCs) might alter the behavioural response of mice in stress-related paradigms and cognitive tasks.

This information has been contributed by Professor Karl.

Current Projects

Title: Cannabidiol (CBD): A novel therapeutic for Alzheimer's disease
Funder:
  • National Health and Medical Research Council (ACRG)
Western Researchers: Tim Karl
Years: 2018-01-01 - 2021-12-31
ID: P00023983
Title: Developing insight into the molecular origins of familial and sporadic frontotemporal dementia and amyotrophic lateral sclerosis [via Macquarie Uni]
Funder:
  • National Health and Medical Research Council (ACRG)
  • National Health and Medical Research Council (ACRG)
Western Researchers: Tim Karl and Yossi Buskila
Years: 2016-01-01 - 2020-12-31
ID: P00023118
Title: Defining the spatial and temporal regulation of neurite branching [via UNSW]
Funder:
  • Australian Research Council (ACRG)
Western Researchers: Tim Karl
Years: 2018-01-01 - 2020-12-31
ID: P00023860
Title: Cannabidiol: a new preventative treatment for schizophrenia?
Funder:
  • Australian Rotary Health (non ACRG)
Western Researchers: Rose Chesworth and Tim Karl
Years: 2018-01-01 - 2021-12-31
ID: P00024826

Previous Projects

Title: Gene-Environment Interactions in Brain Disorders
Funder:
  • National Health and Medical Research Council (ACRG)
Western Researchers: Tim Karl
Years: 2016-02-01 - 2016-12-31
ID: P00023116
Title: Neuregulin 1 Type III Overexpression and Schizophrenia
Funder:
  • National Health and Medical Research Council (ACRG)
Western Researchers: Tim Karl
Years: 2016-02-01 - 2020-01-31
ID: P00023117
Title: To gain a deeper understanding of the molecular origins of dementia and to develop new therapeutic compounds
Funder:
  • Rebecca L Cooper Medical Research Foundation Ltd
Western Researchers: Tim Karl
Years: 2016-01-24 - 2016-12-31
ID: P00023005
Title: The therapeutic potential of cannabidiol (CBD) in mouse models of Alzheimer's disease
Funder:
  • Alzheimer's Australia Dementia Research Foundation (ACRG)
Western Researchers: Tim Karl
Years: 2017-03-01 - 2019-09-01
ID: P00023825
Title: Targeting the synaptic actin cytoskeleton in Alzheimer's Disease [via UNSW]
Funder:
  • National Health and Medical Research Council (ACRG)
Western Researchers: Tim Karl
Years: 2018-03-28 - 2018-12-31
ID: P00024938

Media

Title: ABC Catalyst Documentary
Description: Medicinal Cannabis
Title: Sydney Morning Herald
Description: CBD as a treatment option for dementia.

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