Pertti Panula Professor of Biomedicine, Research Director Biomedicum Helsinki P.O. Box 63, FIN-00014 University of Helsinki Phone: +358-9-191 25263 Fax: +358-9-191 25261 E-mail: pertti-dot-panula-at-helsinki-dot-fi

The modulatory neurotransmitter systems include several aminergic and peptidergic neuron systems and their long projections in the vertebrate brain. These transmitters use a large number of G protein-coupled receptors, which share signal transduction systems in cells. In addition to regulating key physiological functions, many of these systems are involved in important human neurodegenerative diseases.  Our research focuses on identification and functional roles of new modulatory systems, and their functional roles in brain diseases. A particular target is the histaminergic system, which has important interactions with other aminergic (e.g. dopaminergic) and peptidergic systems in regulation of, for instance, e.g. sleep, diurnal rhythms, feeding, and addiction. Using new algorithms, novel receptors were identified in databases. They were cloned in several species and expression analyses suggest that they regulate important functions.  New methods were developed to use zebrafish in combined studies of complex neuronal systems. Confocal and two-photon imaging systems allow three-dimensional imaging of whole neurotransmitter systems in the zebrafish brain at a time when the fish already display complex behaviors. Quantitative behavioral analysis systems were developed to simultaneously analyze the behaviour of up to 100 fish. Identification and cloning of fish orthologs of important human disease genes with poorly known functions and translation inhibition and identification of mutant zebrafish are followed by phenotypic analysis using the new imaging and behavioural methods.  The methods created in the project also allow use of zebrafish in the development of new drugs for central nervous system disorders, including those related to motor functions, anxiety-related behaviour, and memory.

Personnel
Group leader: Professor, Research Director Pertti Panula, MD, PhD
Post-doctoral fellows: Yu-Chia Chen, PhD; Kaj Karlstedt, PhD; Hisaaki Kudo, PhD; Yaroslav Lyubimov, PhD; Saara Nuutinen, PhD
Fish Manager: Henri Koivula, BSc
Graduate students: Raphaela Kaisler, MSc; Ilmari Määttänen, MSc; Madhusmita Priyadarshini, MSc; Stanislav Rozov, MSc; Ville Sallinen, MD; Maria Sundvik, MSc
Undergraduate students: Tiia Ojala, Gabija Toleikyte
Technicians: Anna Lehtonen BSc; Susanna Norrbacka

Selected publications
Haas, H.L., and Panula, P. (2003). The role of histamine and the tuberomamillary nucleus in the brain. Nat. Rev. Neurosci. 4: 121-130.

Karlstedt, K., Åhman, M., Soinila, S., and Panula, P. (2003). Expression of histamine H3 receptor during development and adult brown adipose tissue suggests novel roles for histamine in thermoregulation. Mol. Cell. Neurosci. 24: 614-622.

Engström, M., Brandt, A., Wurster, S., Savola, J.-M., and Panula, P. (2003). Prolactin-releasing peptide has high affinity and efficacy on the neuropeptide FF2 receptor. J. Pharmacol. Exp. Ther. 305: 825-832.

Kalliomäki, M., Pertovaara, A., Brandt, A., Wei, H., Pietilä, P., Kalmari, J., Xu, M., Kalso, E., and Panula, P. (2004). Prolactin-releasing peptide affects pain, allodynia and autonomic reflexes through medullary mechanisms. Neuropharmacology 46: 412-424.

Kaslin, J., Nystedt, J.M., Östergård, M., Peitsaro, N., and Panula, P. (2004). The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J. Neurosci. 24: 2678-2689.

Anichtchik, O.V., Kaslin, J., Peitsaro, N., Scheinin, M., and Panula, P. (2004). Neurochemical and behavioral changes in zebrafish Danio rerio after systemic administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Neurochem. 88: 443-453.

Lintunen, M., Sallmen, T., Karlstedt, K., and Panula, P. (2005). Systemic kainic acid induces profound transient changes in the limbic histaminergic system. Neurobiol. Dis. 20: 155-169.

Kukko-Lukjanov, T.-K., Soini, S., Michelsen, K.A., Panula, P., and Holopainen, I.E. (2006). Histaminergic neurons protect the developing hippocampus from kainic acid-induced neuronal damage in an organotypic co-culture system. J. Neurosci. 26: 1088-1097.

Peitsaro, N., Sundvik, M., Anichtchik, O.V., Kaslin, J., and Panula, P. (2007). Identification of zebrafish histamine H1, H2 and H3 receptors and effects of histaminergic ligands on behavior. Biochem. Pharmacol. 73:1205-14.

Bongers, G., Sallmen, T., Passani, M.B., Mariottini, C., Wendelin, D., Lozada, A., Marle, A., Navis, M., Blandina, P., Bakker, R.A., Panula, P., and Leurs, R. (2007). The Akt/GSK-3beta axis as a new signaling pathway of the histamine H(3) receptor. J. Neurochem. 103: 248-258.