Pertti Panula group


Research People Selected publications

 

Pertti Panula
Professor of Biomedicine, Research Director
Neuroscience Center and Institute of Biomedicine, Faculty of Medicine
P.O. Box 63, FI-00014 University of Helsinki
Phone: 25263 (internal), +358 40 5922 323
E-mail: pertti.panula at helsinki.fi


The modulatory neurotransmitters activate G protein-coupled receptors, which share signal transduction systems in cells. In addition to regulating key physiological functions, these systems are involved in human mental and neurological diseases. We are particularly interested in the histaminergic system, which interacts with other systems such as the dopaminergic, GABAergic and glutamatergic ones in regulation of, for instance, sleep, diurnal rhythms, feeding, and addiction.

In a mouse model, lack of histamine in the brain of histidine decarboxylase-deficient mice was associated with an altered ethanol-induced locomotor response. H3 receptor antagonists inhibited the ethanol-evoked conditioned place preference whereas an agonist did not. Acute stimulatory response by ethanol was also modulated by H3 receptor ligands. An antagonist increased ethanol activation, whereas agonist pretreatment diminished it. The inhibition of ethanol reward by H3 receptor antagonism implies that H3 receptor is a potential target to suppress compulsory ethanol seeking. In a postmortem human study, H3 receptor radioligand binding was higher in the prefrontal cortex of schizophrenic brains than in control subjects, suggesting that histamine through this receptor may regulate cortical functions important in psychiatric diseases.

Zebrafish has become a useful tool to study the interactions of the modulatory neurotransmitter systems. The two tyrosine hydroxylases (th1 and th2) in zebrafish brain showed complementary expression patterns. Translation inhibition of the PARK6 gene (PINK1) important in early-onset Parkinson’s disease led to decreased neuron numbers in dopaminergic cell groups expressing either th1 or th2. A decline in neuron numbers was associated with decreased locomotor activity of the fish, suggesting that these neurons are functionally important. Inhibition of PINK1 translation also rendered the fish sensitive to subeffective doses of MPTP, indicating interactions of genetic and environmental factors relevant in Parkinson’s disease. Using microarray analyses, several novel signaling pathways related to PINK1 knockdown were identified and verified functionally.  Histaminergic neurons are found around the largest th2 neuron group in zebrafish brain. Knocking down histidine decarboxylase abolished the dark induced flash response of larval fish, and decreased the number of hypocretin neurons.  The effect was mimicked by histamine H1 receptor antagonists, suggesting that histamine through this receptor controls the hypocretin system.